Journal articles: 'Somatic amplification'

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Barsky, A. J., J. D. Goodson, R. S. Lane, and P. D. Cleary. "The amplification of somatic symptoms." Psychosomatic Medicine 50, no. 5 (September 1988): 510–19. http://dx.doi.org/10.1097/00006842-198809000-00007.

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McKenzie, Kirsten J., Ellen Poliakoff, Stephen Puntis, Adam Lawrence, Richard J. Brown, and Donna M. Lloyd. "Investigations into visually-induced somatic amplification." Seeing and Perceiving 25 (2012): 165. http://dx.doi.org/10.1163/187847612x647955.

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Studies into tactile detection have found that a simultaneous light stimulus affects judgments of the presence or absence of a near threshold tactile stimulus, leading to higher numbers of false alarms, whereby participants report feeling a touch in the absence of a stimulus, as well as modest improvements in tactile sensitivity (Lloydet al., 2008; McKenzieet al., 2010, 2012). Anecdotally, the reported intensity of the bi-modal stimuli was also enhanced — an effect that was investigated in the current studies. In Experiment 1 participants discriminated between ‘weak’ and ‘strong’ tactile stimuli, which were accompanied by a light flash on 50% of trials. We observed a bias towards classifying light-present vibrations as ‘strong’ regardless of signal strength, as well as some evidence for improved accuracy in discrimination. In Experiment 2, participants gave a subjective intensity rating on a 6-point scale, which showed an increase in magnitude ratings for both ‘weak’ and ‘strong’ vibrotactile stimuli when the light was present. This shows that a simultaneous light can both improve tactile discrimination and lead to both types of tactile stimulus being rated as stronger. Primary somatosensory cortex may underlie these effects, as it receives direct projections from visual cortex and indirect projections from association areas of the brain. However, it is as yet unclear whether or not these effects are due to the same underlying mechanism, or at which processing stage they occur. Therefore, we are currently exploring the neural underpinnings of this amplification effect using both fMRI and EEG.

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Ramel, C., H. Cederberg, J. Magnusson, E. Vogel, A. T. Natarajan, L. H. Mullender, J. M. Nivard, et al. "Somatic recombination, gene amplification and cancer." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 353, no. 1-2 (June 1996): 85–107. http://dx.doi.org/10.1016/0027-5107(95)00243-x.

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Kosturek, Anna, Robert J. Gregory, Anthony J. Sousou, and Paula Trief. "Alexithymia and Somatic Amplification in Chronic Pain." Psychosomatics 39, no. 5 (September 1998): 399–404. http://dx.doi.org/10.1016/s0033-3182(98)71298-8.

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Minarikova, Petra, Lucie Benesova, Tereza Halkova, Barbora Belsanova, Inna Tuckova, Frantisek Belina, Ladislav Dusek, Miroslav Zavoral, and Marek Minarik. "Prognostic Importance of Cell Cycle Regulators Cyclin D1 (CCND1) and Cyclin-Dependent Kinase Inhibitor 1B (CDKN1B/p27) in Sporadic Gastric Cancers." Gastroenterology Research and Practice 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/9408190.

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Background. Gastric cancer is known for a notable variety in the course of the disease. Clinical factors, such as tumor stage, grade, and localization, are key in patient survival. It is expected that molecular factors such as somatic mutations and gene amplifications are also underlying tumor biological behavior and may serve as factors for prognosis estimation.Aim. The purpose of this study was to examine gene amplifications from a panel of genes to uncover potential prognostic marker candidates.Methods. A panel of gene amplifications including 71 genes was tested by multiplex ligation-dependent probe amplification (MLPA) technique in 76 gastric cancer samples from a Caucasian population. The correlation of gene amplification status with patient survival was determined by the Kaplan-Meier method.Results. The amplification of two cell cycle regulators,CCND1andCDKN1B, was identified to have a negative prognostic role. The medial survival of patients with gastric cancer displaying amplification compared to patients without amplification was 192 versus 725 days forCCND1(P=0.0012) and 165 versus 611 days forCDKN1B(P=0.0098).Conclusion. Gene amplifications ofCCND1andCDKN1Bare potential candidates to serve as prognostic markers for the stratification of patients based on the estimate of survival in the management of gastric cancer patients.

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Wang, X., X. Li, L. Zhang, S. H. Wong, M. H. T. Wang, G. Tse, R. Z. W. Dai, et al. "Oncogenes expand during evolution to withstand somatic amplification." Annals of Oncology 29, no. 11 (November 2018): 2254–60. http://dx.doi.org/10.1093/annonc/mdy397.

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Berezovsky, A. D., A. Transou, S. Irtenkauf, L. Poisson, K. Hank Wu, T. Mikkelsen, and A. deCarvalho. "P11.54 Identification of PDGFRA and MYC(N) as somatic driver genes in Glioblastoma." Neuro-Oncology 21, Supplement_3 (August 2019): iii55—iii56. http://dx.doi.org/10.1093/neuonc/noz126.200.

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Abstract BACKGROUND Somatic oncogene amplification happens frequently in glioblastoma (GBM). The second most frequently amplified gene encoding receptor tyrosine kinases in GBMs is platelet derived growth factor alpha (PDGFRA) (15%). In contrast, MYC and MYCN amplification occurs in 1.6% and 2.9%, respectively. Our goal was to characterize the role of PDGFRɑ and Myc in GBM. MATERIAL AND METHODS Neurosphere cultures were implanted in cohorts of 10–15 nude mice. 5 PDX lines, presenting median survival of 29–59 days were classified as short survivors, and 5 lines with median survival between 104–134 days classified as long survivors. Total RNA was extracted from PDX terminal tumors (3 biological replicates) and sequenced in a paired-end read format. Mouse reads were filtered out using Xenome. MYC and PDGFRA expression patterns were analyzed in tissue microarrays representing duplicated samples from 40 glioma neurosphere-derived PDX lines by IHC (1 anaplastic oligodendroglioma, 8 recurrent GBM with 2 newly diagnosed/recurrent pairs). Normalized staining intensity (MI) and area (A) were quantified using Fiji/ImageJ. RESULTS PDGFRA, MYC, MYCN gene amplifications were represented in a molecularly diverse panel of GBM patient-derived cancer stem-like cells (CSC) and orthotopic mouse xenografts (PDX). Transforming to a normal distribution (log10), 4/13 of cell lines had a PDGFRA mRNA expression (RPKM) higher than 1.5. Similarly, one PDX line had a staining index of greater than 10, 11 (27.5%) had an index between 5–10. The range of intra-tumoral variance, represented by standard deviation, was 0.09–24.25 highlighting the heterogeneity of PDGFRɑ expression. PDGFRɑ phosphorylation (Y754) did not differ between 8 cell lines cultured in NMGF, but deviated in alternate medias without growth factors, supplemented with FBS. In comparison, MYC(N) mRNA expression is only elevated in the context of a known amplification. Furthermore, a a MYC activity signature consisting of 18 target genes was only evident in the 5 amplified CSC lines. Taking advantage of genomic heterogeneity, we have isolated subclones lacking PDGFRA amplification from a PDGFRA amplified GBM CSC. The absence of PDGFRA amplification reduced the self-renewal potential to 37% of the PDGFRA amplified cell population (p=0.001) in clone 1 and 57% in clone 2 (p=0.013). Pertaining to determinants of in vivo survival, MYC was altered in 80% of short survivors (2/5 MYC, 2/5 MYCN amplification) and in 0% of long survivors. Myc signature was highly correlated with in vivo survival (Pearsons’ corr. = -0.77) and MYC gene expression was correlated with in vivo TMZ resistance (corr. = 0.7). CONCLUSION These results suggest that PDGFRɑ expression and activity can occur in the absence of gene amplification, while Myc activity is dependent on gene amplification. Both oncogenes drive oncogenic pathways that should be explored as therapeutic targets.

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Raikar, S. V., C. Bryant, R. Braun, A. J. Conner, and M. C. Christey. "Whole genome amplification from plant cell colonies of somatic hybrids using strand displacement amplification." Plant Biotechnology Reports 1, no. 3 (July 12, 2007): 175–77. http://dx.doi.org/10.1007/s11816-007-0026-3.

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Brocca, Ginevra, Beatrice Poncina, Alessandro Sammarco, Laura Cavicchioli, and Massimo Castagnaro. "KIT Somatic Mutations and Immunohistochemical Expression in Canine Oral Melanoma." Animals 10, no. 12 (December 10, 2020): 2370. http://dx.doi.org/10.3390/ani10122370.

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Canine oral melanoma (COM) is an aggressive neoplasm with a low response to therapies, sharing similarities with human mucosal melanomas. In the latter, significant alterations of the proto-oncogene KIT have been shown, while in COMs only its exon 11 has been adequately investigated. In this study, 14 formalin-fixed, paraffin-embedded COMs were selected considering the following inclusion criteria: unequivocal diagnosis, presence of healthy tissue, and a known amplification status of the gene KIT (seven samples affected and seven non-affected by amplification). The DNA was extracted and KIT target exons 13, 17, and 18 were amplified by PCR and sequenced. Immunohistochemistry (IHC) for KIT and Ki67 was performed, and a quantitative index was calculated for each protein. PCR amplification and sequencing was successful in 97.62% of cases, and no single nucleotide polymorphism (SNP) was detected in any of the exons examined, similarly to exon 11 in other studies. The immunolabeling of KIT was positive in 84.6% of the samples with a mean value of 3.1 cells in positive cases, yet there was no correlation with aberration status. Our findings confirm the hypothesis that SNPs are not a frequent event in KIT activation in COMs, with the pathway activation relying mainly on amplification.

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Joyce, Bryan S., and Pablo A. Tarazaga. "A study of active artificial hair cell models inspired by outer hair cell somatic motility." Journal of Intelligent Material Systems and Structures 28, no. 6 (July 28, 2016): 811–23. http://dx.doi.org/10.1177/1045389x16657425.

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The cochlea displays an important, nonlinear amplification of sound-induced oscillations. In mammals, this amplification is largely powered by the somatic motility of the outer hair cells. The resulting cochlear amplifier has three important characteristics useful for hearing: an amplification of responses from low sound pressures, an improvement in frequency selectivity, and an ability to transduce a broad range of sound pressure levels. These useful features can be incorporated into designs for active artificial hair cells, bio-inspired sensors for use as microphones, accelerometers, or other dynamic sensors. The sensor consists of a cantilever beam with piezoelectric actuators. A feedback controller applies a voltage to the actuators to mimic the outer hair cells’ somatic motility. This article describes three control laws for an active artificial hair cell inspired by models of the outer hair cells’ somatic motility. The first control law is based on a phenomenological model of the cochlea while the second and third models incorporate physiological aspects of the biological cochlea to further improve sensor performance. Simulations show that these models qualitatively reproduce the key aspects of the mammalian cochlea, namely, amplification of oscillations from weak stimuli, higher quality factors, and a wider input dynamic range.

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Muramatsu, Kumiko, Hitoshi Miyaoka, Yoshiyuki Muramatsu, Katsuya Fuse, Fumitoshi Yoshimine, Kunitoshi Kamijima, Fumitake Gejyo, and Koji Sakurai. "The amplification of somatic symptoms in upper respiratory tract infections." General Hospital Psychiatry 24, no. 3 (May 2002): 172–75. http://dx.doi.org/10.1016/s0163-8343(02)00177-9.

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Bridou, Morgiane, and Colette Aguerre. "Validity of the French form of the somatosensory amplification scale in a non-clinical sample." Health Psychology Research 1, no. 1 (March 22, 2013): 11. http://dx.doi.org/10.4081/hpr.2013.668.

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The <em>SomatoSensory Amplification Scale</em> (SSAS) is a 10-item self-report instrument designed to assess the tendency to detect somatic and visceral sensations and experience them as unusually intense, toxic and alarming. This study examines the psychometric properties of a French version of the SSAS in a non-clinical population and, more specifically, explores its construct, convergent and discriminant validities. The SSAS was completed by 375 university students, together with measures of somatization propensity (SCL-90-R somatization subscale) and trait anxiety (STAI Y form). The results of principal component and confirmatory factor analyses suggest that the French version of the SSAS evaluates essentially a single, robust factor (Somatosensory amplification) and two kinds of somatic sensitivity (Exteroceptive sensitivity and Interoceptive sensitivity). Somatosensory amplification correlated with somatization tendency and anxiety propensity. These results encourage further investigations in French of the determinants and consequences of somatosensory amplification, and its use as a therapeutic strategy.

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Hersey, Peter, Jessamy Tiffen, Stuart Gallagher, and Fabian Filipp. "Somatic copy number amplification and activating somatic mutations of EZH2 Y641 drive melanoma by epigenetic remodeling." Journal of Clinical Oncology 33, no. 15_suppl (May 20, 2015): e22072-e22072. http://dx.doi.org/10.1200/jco.2015.33.15_suppl.e22072.

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Lakhlani, Vrushant, and Kirsten J. McKenzie. "Somatosensory amplification and illusory tactile sensations." Seeing and Perceiving 25 (2012): 34. http://dx.doi.org/10.1163/187847612x646569.

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Experimental studies have demonstrated that it is possible to induce convincing bodily distortions in neurologically healthy individuals, through cross-modal manipulations; such as the rubber hand illusion (Botvinick and Cohen, 1998), the parchment skin illusion (Jousmaki and Hari, 1998) and the Somatic Signal Detection Task (SSDT; Lloydet al., 2008). It has been shown previously with the SSDT that when a tactile stimulus is presented with a simultaneous light flash, individuals show both increased sensitivity to the tactile stimulus, and the tendency to report feeling the stimulus even when one was not presented; a tendency which varies greatly between individuals but remains constant over time within an individual (McKenzieet al., 2010). Further studies into tactile stimulus discrimination using the Somatic Signal Discrimination Task (SSDiT) have also shown that a concurrent light led to a significant improvement in people’s ability to discriminate ‘weak’ tactile stimuli from ‘strong’ ones, as well as a bias towards reporting any tactile stimulus as ‘strong’ (Poliakoffet al., in preparation), indicating that the light may influence both early and later stages of processing. The current study investigated whether the tendency to report higher numbers of false alarms when carrying out the SSDT is correlated with the tendency to experience higher numbers of cross-modal ‘enhancements’ of weak tactile signals (leading to classifications of ‘weak’ stimuli as strong, and ‘strong’ stimuli as ‘stronger’). Results will be discussed.

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Page, Karen, David S. Guttery, Daniel Fernandez-Garcia, Allison Hills, Robert K. Hastings, Jinli Luo, Kate Goddard, et al. "Next Generation Sequencing of Circulating Cell-Free DNA for Evaluating Mutations and Gene Amplification in Metastatic Breast Cancer." Clinical Chemistry 63, no. 2 (February 1, 2017): 532–41. http://dx.doi.org/10.1373/clinchem.2016.261834.

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Abstract BACKGROUND Breast cancer tissues are heterogeneous and show diverse somatic mutations and somatic copy number alterations (CNAs). We used a novel targeted next generation sequencing (NGS) panel to examine cell-free DNA (cfDNA) to detect somatic mutations and gene amplification in women with metastatic breast cancer (MBC). METHODS cfDNA from pretreated patients (n = 42) and 9 healthy controls were compared with matched lymphocyte DNA by NGS, using a custom 158 amplicon panel covering hot-spot mutations and CNAs in 16 genes, with further validation of results by droplet digital PCR. RESULTS No mutations were identified in cfDNA of healthy controls, whereas exactly half the patients with metastatic breast cancer had at least one mutation or amplification in cfDNA (mean 2, range 1–6) across a total of 13 genes. Longitudinal follow up showed dynamic changes to mutations and gene amplification in cfDNA indicating clonal and subclonal response to treatment that was more dynamic than cancer antigen 15-3 (CA15-3). Interestingly, at the time of blood sampling disease progression was occurring in 7 patients with erb-b2 receptor tyrosine kinase 2 (ERBB2) gene amplification in their cfDNA and 3 of these patients were human epidermal growth factor receptor 2 (HER2) negative at diagnosis, suggesting clonal evolution to a more aggressive phenotype. Lastly, 6 patients harbored estrogen receptor 1 (ESR1) mutations in cfDNA, suggesting resistance to endocrine therapy. Overall 9 of 42 patients (21%) had alterations in cfDNA that could herald a change in treatment. CONCLUSIONS Targeted NGS of cfDNA has potential for monitoring response to targeted therapies through both mutations and gene amplification, for analysis of dynamic tumor heterogeneity and stratification to targeted therapy.

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Góomez-Seguíi, Inées, Hideki Makishima, Andres Jerez, Kenichi Yoshida, Bartlomiej P. Przychodzen, Satoru Miyano, Yuichi Shiraishi, et al. "Novel Recurrent Mutations in the Ras-Like GTP-Binding Gene Rit1 in Myeloid Malignancies." Blood 120, no. 21 (November 16, 2012): 558. http://dx.doi.org/10.1182/blood.v120.21.558.558.

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Abstract Abstract 558 In addition to chromosomal and epigenetic abnormalities, somatic mutations constitute key pathogenic lesions in myeloid neoplasms. Individual somatic mutations or various combinations may be both valuable prognostic markers and targets for new rational therapies. Among them, RAS family genes are ubiquitous oncogenes associated with various cancers. Recurrent canonical mutations in the nucleotide binding domains in NRAS and KRAS result in constitutively activated proteins. In myeloid neoplasms, RAS mutations convey a poor prognosis and are often found in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and, rarely, myeloproliferative neoplasms (MPN). We applied whole exome sequencing to paired germline vs. leukemia samples in 65 cases of MDS, 36 MDS/MPN and 32 sAML. We focused our study on the RAS protein superfamily of small GTPases and identified mutations in 3% and 6% of KRAS and NRAS, respectively. Most significantly, we identified somatic recurrent mutations in the F82 residue of Ras-like without CAAX1 (RIT1) gene in 2 patients with chronic myelomonocytic leukemia (CMML) and secondary AML (sAML), respectively. We confirmed the somatic nature of both mutations in sorted CD3+ cells from each patient (pt). RIT1 gene encodes a member of Ras-related GTPases, involved in the p38 MAPK and AKT signaling pathway that mediates cellular survival in response to stress. RIT1 gene amplification has been found in 26% of hepatocellular carcinoma. However, neither amplification nor mutations of this gene have been reported in myeloid malignancies. We thus focused this line of experimentation on this somatic mutation. To establish clinical associations we further studied a cohort of 322 patients with various myeloid malignancies by Sanger sequencing and detected somatic RIT1 mutations in an additional 6 (2%) cases. All mutations were located in exon 5, in the 81 and 82 residues, which encode the switch II domain of this protein, an effector region very close to the GTP-binding site G3, and which is highly conserved among species. Among the 8 mutant cases, 5 (63%) pts had CMML, resulting in a higher frequency of mutations in this subcohort of pts (5 out of 57 CMML, 9%). The other 3 mutations were found in one primary (p)AML (M5b subtype) (1 out of 58 pAML, 2%) and two high-grade MDS, one refractory anemia with excess blasts (RAEB)-2 and one sAML(RAEB-T in the FAB-classification) (2 out of 80, 2.5%). RIT1 mutations were heterozygous in all cases except for one case with trisomy 1 and duplication of the mutant allele. In the cases of WES, we estimated an allelic frequency of ∼35%, consistent with the presence of a heterozygous mutation in ∼70% of sample cells. Because of the large size of the clone and serial samples showing RIT1 mutation since the time of initial diagnosis, it is likely that RIT1 may be of ancestral origin. As RAS-family gene amplifications have been described in cancer, we also studied the presence of amplifications of the RIT1 locus (1q22) by SNP-A. We found 10 cases characterized by a gain involving the RIT1 region (1q21.1-q44): 4 (40%) cases had a diagnosis of CMML, 4 (40%) had myelofibrosis, whereas the remaining patients had MDS (one RAEB-1 and a RA). Quantitative RT-PCR showed RIT1 overexpression in mutants and in patients with 1q amplification (median normalized relative ratio 0,51 and 0,40, respectively) compared to patients with wild type RIT1 and no amplification in 1q (median normalized relative ratio 0,15; P=.039). We theorized that activating RIT1 mutations may constitute a suitable therapeutic target. Because AKT inhibitors can block AKT phosphorylation and therefore reverse the antiapoptotic effect of mutant RIT1, we tested whether AKT inhibitor V (Triciribine) can selectively abrogate the growth of primary cells with RIT1 mutation. In in vitro suspension cultures, a 65% of reduction proliferation was observed with significant effects even at 0.1μM concentrations. In sum, somatic recurrent RIT1 mutations are novel lesions involved in the molecular pathogenesis of myeloid cancers, presumably early in the development of the disease. Moreover, amplifications of RIT1 also lead to overexpression of this Ras-like GTP-ase. Specifically, these abnormalities appear to be more frequent in patients with CMML, but also can be found in other types of MDS. Disclosures: Makishima: Scott Hamilton CARES Initiative: Research Funding. Maciejewski:NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding.

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Patel, A., R. Schwab, Y. T. Liu, and V. Bafna. "Amplification and thrifty single-molecule sequencing of recurrent somatic structural variations." Genome Research 24, no. 2 (December 4, 2013): 318–28. http://dx.doi.org/10.1101/gr.161497.113.

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Barrineau, Mary Jon, Steven H. Zarit, Heather A. King, Erin S. Costanzo, and David M. Almeida. "Daily well-being of cancer survivors: the role of somatic amplification." Psycho-Oncology 23, no. 9 (February 26, 2014): 1027–33. http://dx.doi.org/10.1002/pon.3509.

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Boone, Dianna, and Shin Ye Kim. "Family Strain, Depression, and Somatic Amplification in Adults with Chronic Pain." International Journal of Behavioral Medicine 26, no. 4 (June 24, 2019): 427–36. http://dx.doi.org/10.1007/s12529-019-09799-y.

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Makishima, Hideki, Hideki Muramatsu, Asahito Hama, Ramon V. Tiu, Yuka Sugimoto, Mikkael A. Sekeres, Yogen Saunthararajah, Michael A. McDevitt, Seiji Kojima, and Jaroslaw P. Maciejewski. "A High Resolution Analysis of Chromosome 21 Amplification In Myeloid Malignancies Reveals An Association with a Specific Cytogenetic Subgroup and Enhanced ERG Gene Expression." Blood 116, no. 21 (November 19, 2010): 1687. http://dx.doi.org/10.1182/blood.v116.21.1687.1687.

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Abstract Abstract 1687 Genetic alterations including chromosomal translocation, somatic mutation, and gene amplification are thought to play a key role in oncogenesis. Gains of whole or segmental chromosome 21 (Ch21) are observed in many types of myeloid malignancies and are often associated with acute megakaryoblastic leukemia (AMKL). In Down syndrome, transient abnormal myelopoiesis and acute lymphoblastic leukemia can be observed, but the prevalence of AMKL is striking. In rare Down syndrome patients, a subcytogenetic Ch21 minimal amplified region is observed and always found to include ERG as well as the RUNX1 gene locus. Recently, gain of ERG gene copy number has been demonstrated to induce leukemia in mouse models and mutations in RUNX1 have been reported in patients with myeloid malignancies with somatic trisomy 21. The pathogenic gene(s) driving malignant disease in congenital and/or somatic gain of Ch21 are poorly understood. We applied high resolution single nucleotide polymorphism array (SNP-A) to study whether small copy number gains are present on Ch21, which cannot be seen by metaphase cytogenetics. We also tested for potential synergistic karyotypic abnormalities in the patients with gain of Ch21 gene segments. We screened a large cohort of 522 patients with myeloid malignancies by SNP-A platform, and detected 36 events that included whole or partial amplification of Ch21 in 32 cases (6%). The affected length was between 215,063 and 46,944,323 bp and the average was 30,732,002. These include 13 congenital lesions (AMKL evolving in Down syndrome), and 23 somatic alterations. Among the AMKL cohort of 34 cases, gains of Ch21 were observed in 15/25 (60%) juvenile and 2/9 (22%) adult cases. A minimal consensus amplification region was defined from nt38637816 to nt38852879 on Ch21 and this region included ERG. Amplification of ERG was identified in 30/36 of the Ch21 gain lesions studied. Although we sequenced all exons of the ERG gene in all cases with Ch21 gain, no mutation was detected. Based on the possibility that gene amplification leads to increased gene expression, ERG mRNA levels were investigated. CD34+ cells showed the highest ERG expression among hematopoietic cell types. When CD34+ cells from acute myeloid leukemia (AML) patients with somatic trisomy 21, with normal copy of Ch21 and healthy donors were investigated by real time PCR, relative expression of ERG was the highest in trisomy 21 patients among three groups. Based on our previous work and that of others, we tested the mutational status of RUNX1 in the 23 cases with Ch21 amplification that included RUNX1. Mutations were found in 2/23 (9%) accompanied by trisomy 21. No mutation was found in patients with Down syndrome. In one mutant case, a homozygous missense mutation, (L56S) was identified and associated with uniparental trisomy that included RUNX1. The second mutant case (W106L) was in a patient with a 45,XY,-7,i(21)(q10) karyoptype. The mutation was duplicated but was not associated with loss of heterozygosity (LOH). When RUNX1 gene expression in the cases with and without trisomy 21 using CD34 positive bone marrow cells was investigated, no significant difference in relative RUNX1 mRNA levels between trisomy 21 and cases with diploid Ch21 was found. Finally, we evaluated whether additional chromosomal lesions were associated with a gain of Ch21 gene segments. Recurrent losses were detected on chromosome 1, 2, 3, 5, 7, 9, and 17. Deletions of 5q were frequent in the cases with somatic gain of Ch21 (47%; 8/17), while no del5q was detected in the cases with Down syndrome. Conversely, LOH17p (3 uniparental disomies (UPDs) and 2 deletions) was found in both somatic and congenital cases (5/32), with one case of deletion17p associated with a hemizygous p53 mutation. In addition, UPD11q was accompanied by a CBL homozygous mutation in a RAEB case with somatic trisomy 21. Del7q was also observed in both groups (4 in somatic and 3 in congenital cases), including a 7q36.1 microdeletion associated with EZH2 in AMKL with Down syndrome. In sum, our study demonstrates that high resolution SNP-A analysis focused on Ch21 gene segments revealed frequent cryptic somatic gain lesions and a uniparental trisomy. ERG was the sole gene located in the minimally shared gain lesions and is overexpressed in a wild type form in AML cases with somatic trisomy 21. RUNX1 mutations were found in 3 or 2 identical alleles of somatic trisomy 21 cases but are absent in most cases of trisomy 21. Disclosures: No relevant conflicts of interest to declare.

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Qiu, Miao-zhen, Cai-Yun He, and Rui-hua Xu. "Relationship of HER2 alteration and MSI status in colorectal adenocarcinoma." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 121. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.121.

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121 Background: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with MSI-H is an open question. Methods: From February 2017 to February 2020, CRC patients who received tumor specimens next-generation sequencing and detail record of clinic-pathologic information were enrolled. HER2 alteration and its relationship with MSI-H were analyzed. Results: There were totally 55 patients (7.5%) with HER2 alteration including 29 (4.0%) HER2 somatic mutations, 24 (3.3%) HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. For HER2 mutated cases, 48.3% were MSI-H, while none of HER2 amplification cases were MSI-H. MSI-H was found in 5.2% in our cohort and 36.8% MSI-H patients were HER2 mutated. MSI-H had less frequency of lung metastasis. The mPFS for first line chemotherapy was significantly higher in MSS cases than in MSI-H cases, 11.5 months vs 3.5 months, P = 0.032. MSI-H patients with HER2 mutation had significantly worse mPFS for PD-1 antibody than those without HER2 alteration, P = 0.036. Conclusions: High MSI-H rate is found in HER2 mutated cases but no MSI-H in HER2 amplification cases. MSI-H patients with HER2 mutated had worse PFS for PD-1 antibody than those without.

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Gupta, Samir, Bhavana Varshney, Shambhabi Chatterjee, and Krishanu Ray. "Somatic ERK activation during transit amplification is essential for maintaining the synchrony of germline divisions in Drosophila testis." Open Biology 8, no. 7 (July 2018): 180033. http://dx.doi.org/10.1098/rsob.180033.

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Transit amplification (TA) of progenitor cells maintains tissue homeostasis by balancing proliferation and differentiation. In Drosophila testis, the germline proliferation is tightly regulated by factors present in both the germline and the neighbouring somatic cyst cells (SCCs). Although the exact mechanism is unclear, the epidermal growth factor receptor (EGFR) activation in SCCs has been reported to control spermatogonial divisions within a cyst, through downstream activations of Rac1-dependent pathways. Here, we report that somatic activation of the mitogen-activated protein kinase (Rolled/ERK) downstream of EGFR is required to synchronize the mitotic divisions and regulate the transition to meiosis. The process operates independently of the Bag-of-marble activity in the germline. Also, the integrity of the somatic cyst enclosure is inessential for this purpose. Together, these results suggest that synchronization of germ-cell divisions through somatic activation of distinct ERK-downstream targets independently regulates TA and subsequent differentiation of neighbouring germline cells.

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Tsoulos, Nikolaos, Eirini Papadopoulou, Vasiliki Metaxa-Mariatou, Georgios Tsaousis, Chrisoula Efstathiadou, Georgia Tounta, Katerina Skapeti, et al. "Molecular profiling of 502 patient cohort with NSCLC using a 27 somatic gene panel." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e23193-e23193. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e23193.

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e23193 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using the Next Generation Sequencing (NGS) technology, has become a key tool for NSCLC patients’ treatment decision and clinical management. Methods: The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq Technology, was evaluated for the analysis of tumor DNA extracted from FFPE (Formalin Fixed Parraffin Embedded) tissue. Furthermore the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. Tumors’ mutation spectrum was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. Results: The panel used for tumor DNA analysis in this study exhibit high rates (100%) of sensitivity, specificity and reproducibility at a mutation frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK ROS1) and 9.4% had an alteration in a gene related to emerging targeted therapies according the NCCN guidelines. These alterations include ERBB2, BRAF and MET mutations, MET amplification and RET rearrangements. The remaining 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or give them access to a clinical trial. Conclusions: Thus the NGS panel validated is a reliable approach of clinical applicability for tumor molecular profile detection in NSCLC patients.

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Milligan-Saville, Josie S., Helen M. Paterson, Emily L. Harkness, Annabel M. Marsh, Mark Dobson, Richard I. Kemp, Richard A. Bryant, and Samuel B. Harvey. "The Amplification of Common Somatic Symptoms by Posttraumatic Stress Disorder in Firefighters." Journal of Traumatic Stress 30, no. 2 (March 8, 2017): 142–48. http://dx.doi.org/10.1002/jts.22166.

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Barrett, Michael T., Brian J. Reid, and Geoffrey Joslyn. "Genotypic analysis of multiple loci in somatic cells by whole genome amplification." Nucleic Acids Research 23, no. 17 (1995): 3488–92. http://dx.doi.org/10.1093/nar/23.17.3488.

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KORBON, GREGG A., DOUGLAS E. DeGOOD, MARK E. SCHROEDER, DAVID P. SCHWARTZ, and MICHAEL S. SHUTTY. "The Development of a Somatic Amplification Rating Scale for Low-back Pain." Spine 12, no. 8 (October 1987): 787–91. http://dx.doi.org/10.1097/00007632-198710000-00014.

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Andreasen, Mogens, and John D. C. Lambert. "Somatic amplification of distally generated subthreshold EPSPs in rat hippocampal pyramidal neurones." Journal of Physiology 519, no. 1 (August 1999): 85–100. http://dx.doi.org/10.1111/j.1469-7793.1999.0085o.x.

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Ozias-Akins, Peggy, Zoreh Tabaeizadeh, Daryl R. Pring, and Indra K. Vasil. "Preferential amplification of mitochondrial DNA fragments in somatic hybrids of the Gramineae." Current Genetics 13, no. 3 (March 1988): 241–45. http://dx.doi.org/10.1007/bf00387770.

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Peng, Anthony W., and Anthony J. Ricci. "Somatic motility and hair bundle mechanics, are both necessary for cochlear amplification?" Hearing Research 273, no. 1-2 (March 2011): 109–22. http://dx.doi.org/10.1016/j.heares.2010.03.094.

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Curtin, John A., Klaus Busam, Daniel Pinkel, and Boris C. Bastian. "Somatic Activation of KIT in Distinct Subtypes of Melanoma." Journal of Clinical Oncology 24, no. 26 (September 10, 2006): 4340–46. http://dx.doi.org/10.1200/jco.2006.06.2984.

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Purpose Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed), and skin with chronic sun-induced damage have infrequent mutations in BRAF and NRAS, genes within the mitogen-activated protein (MAP) kinase pathway commonly mutated in melanomas on intermittently sun-exposed skin. This raises the question of whether other aberrations are occurring in the MAP kinase cascade in the melanoma types with infrequent mutations of BRAF and NRAS. Patients and Methods We analyzed array comparative genomic hybridization data from 102 primary melanomas (38 from mucosa, 28 from acral skin, and 18 from skin with and 18 from skin without chronic sun-induced damage) for DNA copy number aberrations specific to melanoma subtypes where mutations in BRAF and NRAS are infrequent. A narrow amplification on 4q12 was found, and candidate genes within it were analyzed. Results Oncogenic mutations in KIT were found in three of seven tumors with amplifications. Examination of all 102 primary melanomas found mutations and/or copy number increases of KIT in 39% of mucosal, 36% of acral, and 28% of melanomas on chronically sun-damaged skin, but not in any (0%) melanomas on skin without chronic sun damage. Seventy-nine percent of tumors with mutations and 53% of tumors with multiple copies of KIT demonstrated increased KIT protein levels. Conclusion KIT is an important oncogene in melanoma. Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden.

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Koo, Kendrick, Dmitri Mouradov, Christopher M. Angel, Tim A. Iseli, David Wiesenfeld, Michael J. McCullough, Antony W. Burgess, and Oliver M. Sieber. "Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients." Cancers 13, no. 5 (March 1, 2021): 1029. http://dx.doi.org/10.3390/cancers13051029.

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Molecular alterations in 176 patients with oral squamous cell carcinomas (OSCC) were evaluated to delineate differences in non-smoking non-drinking (NSND) patients. Somatic mutations and DNA copy number variations (CNVs) in a 68-gene panel and human papilloma virus (HPV) status were interrogated using targeted next-generation sequencing. In the entire cohort, TP53 (60%) and CDKN2A (24%) were most frequently mutated, and the most common CNVs were EGFR amplifications (9%) and deletions of BRCA2 (5%) and CDKN2A (4%). Significant associations were found for TP53 mutation and nodal disease, lymphovascular invasion and extracapsular spread, CDKN2A mutation or deletion with advanced tumour stage, and EGFR amplification with perineural invasion and extracapsular spread. PIK3CA mutation, CDKN2A deletion, and EGFR amplification were associated with worse survival in univariate analyses (p < 0.05 for all comparisons). There were 59 NSND patients who tended to be female and older than patients who smoke and/or drink, and showed enrichment of CDKN2A mutations, EGFR amplifications, and BRCA2 deletions (p < 0.05 for all comparisons), with a younger subset showing higher mutation burden. HPV was detected in three OSCC patients and not associated with smoking and drinking habits. NSND OSCC exhibits distinct genomic profiles and further exploration to elucidate the molecular aetiology in these patients is warranted.

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Patel, Amol, H. P. Singh, Suresh Pandalanghat, Manish Kumar, Bhupesh Guleria, and Shivashankara Swamy Mathighatta Shivarudraiah. "Genomic architecture of gallbladder cancer: Results of a first prospective study." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e16628-e16628. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e16628.

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e16628 Background: Rarity in western countries precluded Gallbladder cancer (GBC) from prospective research. Comprehensive Genomic profiling carries potential to determine oncogenic pathways, driver mutations and possible resistance mechanisms. This study is evaluating the role of comprehensive genomic profiling and role of targeted therapies therein. Methods: This is a single center, prospective, study conducted from Aug2018-Dec2019. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture based comprehensive genomic profiling was performed by Foundation Medicine CDx. Microsatellite instability and PDL1 expression were studied. Results: Median age was 56 years (range:26-83) with male to female ratio of 1:1.6. NGS information was available for 50 patients. ERBB pathway was aberrated in 44% of patients. ERBB2 & ERBB3 amplification was seen in 9(18%) and 2(4%) patients respectively. ERBB2 mutations were present concurrently with amplification in 3 patients. MET amplification was present in 3 (6%) PIK3CA mutations were seen in 14% of cases. PIK3CA mutations were independent of ERBB aberrations. FGFR2 mutation, FGFR2 and FGFR3 amplification was present in one patient each. NF1 and NF2 mutations were seen in three and two patients respectively. Median TMB (n = 39) was 5 mut/Mb with range of 1-14 mut/Mb. PDL1 (n = 31) of ≥ 1% was present in 32% of cases and it ranged from 1-100%. MSI (n = 39) was stable in all cases. Other somatic mutations and/or amplifications are shown in Table. Conclusions: GBC is enriched in 28% of patients with ERBB2 & ERBB3 amplifications and/or mutations. FGFR2 mutation is rare in GBC. PIK3CA aberrations are common. Phase 2 trial of frontline Trastuzumab combined with chemotherapy is ongoing. [Table: see text]

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Berezovsky, Artem, Indrani Datta, Ruicong She, Laura Hasselbach, Laila Poisson, and Ana C. deCarvalho. "OTEH-12. Assessing Adaptive Responses to Loss of Extrachromosomal DNA Amplification." Neuro-Oncology Advances 3, Supplement_2 (July 1, 2021): ii13. http://dx.doi.org/10.1093/noajnl/vdab070.051.

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Abstract Background Oncogene activation through somatic gene amplification happens frequently in GBM, with over 70% of these tumors presenting amplification of at least one putative driver gene, oftentimes in small extrachromosomal circular DNA segments composed of chromatin (ecDNA). A molecularly diverse and representative panel of GBM patient-derived cancer stem-like cells (CSC) and orthotopic mouse xenografts (PDX), which retain the original genomic abnormalities and ecDNA amplifications, was employed to assess adaptive response to the absence of ecDNA amplification. Methods We have isolated ecDNA negative cell populations from two patient-derived models. HF3035 harbors a MET amplification and HF3253 harbors a PDGFRA constitutively active genomic rearrangement and extrachromosomal amplification. We conducted paired, whole RNA-sequencing on 20 HF3253 populations (ecDNA+/-: 6 clones from 3 biological replicate PDXs and 4 clones from 4 in vitro technical replicates) and 12 HF3035 population (ecDNA+/-: 6 clones from 3 biological replicate PDXs). Results Nonparametric differentially expressed gene (DEG) analysis using NOISeqBio (R/Bioconductor), identified 564 differentially expressed genes (482 upregulated in ecDNA(-)) employing a stringent false discovery rate of 0.05. Genes significantly associated with PDGF stimulation, central carbon metabolism, and H3K27me3 were downregulated in ecDNA(-), while genes significantly associated with astrocytic processes, neuronal differentiation, and EGFR signaling were upregulated in ecDNA(-) (EnrichR). We employed an additive linear model with PDX serving as a blocking factor to compare ecDNA+ and ecDNA- populations in both models (R/edgeR). 2071 genes were upregulated in ecDNA+ PDX specimens and 2365 genes were downregulated. Specifically, E2F targets were highly enriched in ecDNA+ populations, in addition to mRNA pre-processing. ecDNA loss primarily targeted glycogen metabolism, NTRK signaling, and inositol phosphate catabolism. Conclusions We have identified PDX-specific and non-specific features to an adaptive response to the loss of ecDNA amplification. Notably, a signature adaptation is an upregulation of seemingly redundant receptor tyrosine kinases.

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Trigiano, R. N., M. C. Scott, and G. Caetano-Anollés. "Arbitrary Signatures from Amplification Profiles (ASAP) Distinguishes Somatic and Radiation-induced Mutations in the `Charm' Series of Chrysanthemum." HortScience 32, no. 3 (June 1997): 500B—500. http://dx.doi.org/10.21273/hortsci.32.3.500b.

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Four chrysanthemum (Dendranthema grandiflora) spontaneous and radiation-induced sports from the cultivar `Charm' and phenotypically differing only in flower color were individually characterized using arbitrary signatures from amplification profiles (ASAP). ASAP analysis is based on a two-step arbitrary primer amplification procedure that produces “fi ngerprints of fingerprints.” In the first step, `Charm', `Dark Charm', `Dark Bronze Charm', `Salmon Charm', and `Coral Charm' were fingerprinted by DNA amplification fingerprinting (DAF) with standard octamer arbitrary primers. Diluted products from three monomorphic fingerprints for each cultivar were subsequently reamplified using four minihairpin decamer primers. Each of the 12 ASAP profiles revealed polymorphic loci that were used to uniquely identify cultivars and estimate genetic relationships. The ASAP technique permits identification of previously genetically indistinguishable plant material and should facilitate marker assisted breeding and protection of ownership rights.

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Schoen, Daniel J., and Stewart T. Schultz. "Somatic Mutation and Evolution in Plants." Annual Review of Ecology, Evolution, and Systematics 50, no. 1 (November 2, 2019): 49–73. http://dx.doi.org/10.1146/annurev-ecolsys-110218-024955.

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Somatic mutations are common in plants, and they may accumulate and be passed on to gametes. The determinants of somatic mutation accumulation include the intraorganismal selective effect of mutations, the number of cell divisions that separate the zygote from the formation of gametes, and shoot apical meristem structure and branching. Somatic mutations can promote the evolution of diploidy, polyploidy, sexual recombination, outcrossing, clonality, and separate sexes, and they may contribute genetic variability in many other traits. The amplification of beneficial mutations via intraorganismal selection may relax selection to reduce the genomic mutation rate or to protect the germline in plants. The total rate of somatic mutation, the distribution of selective effects and fates in the plant body, and the degree to which the germline is sheltered from somatic mutations are still poorly understood. Our knowledge can be improved through empirical estimates of mutation rates and effects on cell lineages and whole organisms, such as estimates of the reduction in fitness of progeny produced by within- versus between-flower crosses on the same plant, mutation coalescent studies within the canopy, and incorporation of somatic mutation into theoretical models of plant evolutionary genetics.

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Trigiano, R. N., M. C. Scott, and G. Caetano-Anollés. "Arbitrary Signatures From Amplification Profiles (ASAP) Distinguishes Somatic and Radiation Induced Mutations in the `Charm' Series of Chrysanthemum." HortScience 32, no. 4 (July 1997): 593C—593. http://dx.doi.org/10.21273/hortsci.32.4.593c.

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Four chrysanthemum (Dendranthema grandiflora) spontaneous and radiation-induced sports from the cultivar `Charm' and phenotypically differing only in flower color were individually characterized using arbitrary signatures from amplification profiles (ASAP). ASAP analysis is based on a two-step arbitrary primer amplification procedure that produces “fingerprints of fingerprints.” In the first step, `Charm', `Dark Charm', `Dark Bronze Charm', `Salmon Charm', and `Coral Charm' were fingerprinted by DNA amplification fingerprinting (DAF) with standard octamer arbitrary primers. Diluted products from three monomorphic fingerprints for each cultivar were subsequently reamplified using four minihairpin decamer primers. Each of the 12 ASAP profiles revealed about 30% polymorphic loci and some were used to uniquely identify cultivars and estimate genetic relationships. The ASAP technique permits identification of previously genetically indistinguishable plant material and should facilitate marker assisted breeding and protection of ownership rights.

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Marsh, Thomas C., Eric S. Cole, and Daniel P. Romero. "The Transition From Conjugal Development to the First Vegetative Cell Division Is Dependent on RAD51 Expression in the Ciliate Tetrahymena thermophila." Genetics 157, no. 4 (April 1, 2001): 1591–98. http://dx.doi.org/10.1093/genetics/157.4.1591.

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Abstract Rad51p, the eukaryotic homolog of the prokaryotic recA protein, catalyzes strand exchange between single- and double-stranded DNA and is involved in both genetic recombination and double-strand break repair in the ciliate Tetrahymena thermophila. We have previously shown that disruption of the Tetrahymena RAD51 somatic macronuclear locus leads to defective germline micronuclear division and that conjugation of two somatic rad51 null strains results in an early meiotic arrest. We have constructed Tetrahymena strains that are capable of RAD51 expression from their parental macronuclei and are homozygous, rad51 nulls in their germline micronuclei. These rad51 null heterokaryons complete all of the early and middle stages of conjugation, including meiosis, haploid nuclear exchange, zygotic fusion, and the programmed chromosome fragmentations, sequence eliminations, and rDNA amplification that occur during macronuclear development. However, the rad51 null progeny fail to initiate the first vegetative cell division following conjugal development. Coincident with the developmental arrest is a disproportionate amplification of rDNA, despite the maintenance of normal total DNA content in the developing macronuclei. Fusion of arrested rad51 null exconjugants to wild-type cells is sufficient to overcome the arrest. Cells rescued by cytoplasmic fusion continue to divide, eventually recapitulating the micronuclear mitotic defects described previously for rad51 somatic nulls.

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Trigiano, R. N., M. C. Scott, and G. Caetano-Anollés. "Genetic Signatures from Amplification Profiles Characterize DNA Mutation in Somatic and Radiation-induced Sports of Chrysanthemum." Journal of the American Society for Horticultural Science 123, no. 4 (July 1998): 642–46. http://dx.doi.org/10.21273/jashs.123.4.642.

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The chrysanthemum (Dendranthema grandiflora Tzvelev.) cultivars `Dark Charm', `Salmon Charm', `Coral Charm' and `Dark Bronze Charm' are either radiation-induced mutants or spontaneous sports of `Charm' and constitute a family or series of plants that primarily differ in flower color. These cultivars, which were difficult to differentiate genetically by DNA amplification fingerprinting (DAF), were easily identified by using arbitrary signatures from amplification profiles (ASAP). Genomic DNA was first amplified with three standard octamer arbitrary primers, all of which produced monomorphic profiles. Products from each of these DNA fingerprints were subsequently reamplified using four minihairpin decamer primers. The 12 primer combinations produced signatures containing ≈37% polymorphic character loci, which were used to estimate genetic relationships between cultivars. Forty-six (32%) unique amplification products were associated with individual cultivars. The number of ASAP polymorphisms detected provided an estimate of the mutation rate in the mutant cultivars, ranging from 0.03% to 1.6% of nucleotide changes within an average of 18 kb of arbitrary amplified DAF sequence. The ASAP technique permits the clear genetic identification of somatic mutants and radiation-induced sports that are genetically highly homogeneous and should facilitate marker assisted breeding and protection of plant breeders rights of varieties or cultivars.

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Freyler, Anett, Zita Kőhegyi, Ferenc Köteles, Gyöngyi Kökönyei, and György Bárdos. "Modern health worries, subjective somatic symptoms, somatosensory amplification, and health anxiety in adolescents." Journal of Health Psychology 18, no. 6 (March 21, 2013): 773–81. http://dx.doi.org/10.1177/1359105313479629.

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Van Bockstal, Mieke R., Marie Colombe Agahozo, Ronald van Marion, Peggy N. Atmodimedjo, Hein F. B. M. Sleddens, Winand N. M. Dinjens, Lindy L. Visser, Esther H. Lips, Jelle Wesseling, and Carolien H. M. van Deurzen. "Somatic mutations and copy number variations in breast cancers with heterogeneous HER2 amplification." Molecular Oncology 14, no. 4 (April 2020): 671–85. http://dx.doi.org/10.1002/1878-0261.12650.

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Kadam, Umesh T., Kelvin Jordan, and Peter R. Croft. "Clinical comorbidity was specific to disease pathology, psychologic distress, and somatic symptom amplification." Journal of Clinical Epidemiology 58, no. 9 (September 2005): 909–17. http://dx.doi.org/10.1016/j.jclinepi.2005.02.007.

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Vijg, Jan, Xiao Dong, and Lei Zhang. "A high-fidelity method for genomic sequencing of single somatic cells reveals a very high mutational burden." Experimental Biology and Medicine 242, no. 13 (July 2017): 1318–24. http://dx.doi.org/10.1177/1535370217717696.

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Postzygotic mutations in somatic cells lead to genome mosaicism and can be the cause of cancer, possibly other human diseases and aging. Somatic mutations are difficult to detect in bulk tissue samples. Here, we review the available assays for measuring somatic mutations, with a focus on recent single-cell, whole genome sequencing methods. Impact statement Somatic mutations cause cancer, possibly other diseases and aging. Yet, very little is known about the frequency of such mutations in vivo, their distribution across the genome, and their possible functional consequences other than cancer. Even in cancer, we do not know the heterogeneity of mutations within a tumor and if seemingly normal cells in its surroundings already have elevated mutation frequencies. Here, we review a new, whole genome amplification system that allows accurate quantification and characterization of single-cell mutational landscapes in human cells and tissues in relation to disease.

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Kealy, David, Simon M. Rice, Gabrielle B. Chartier, and Daniel W. Cox. "Investigating Attachment Insecurity and Somatosensory Amplification, and the Mediating Role of Interpersonal Problems." European Journal of Health Psychology 28, no. 3 (July 2021): 120–30. http://dx.doi.org/10.1027/2512-8442/a000078.

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Abstract. Background: Somatosensory amplification involves perceptual sensitivity to and cognitive-affective interpretation of bodily sensations and external stimuli, contributing to heightened experiences of somatic symptoms. However, little is known about somatosensory amplification in relation to vulnerabilities such as attachment insecurity. Aims: The present study investigated the link between attachment insecurity and somatosensory amplification, including the mediating role of dysfunctional interpersonal behaviors. Method: A sample of 245 adult community members completed the Somatosensory Amplification Scale, Generalized Anxiety Disorder Scale, and abbreviated versions of the Experiences in Close Relationships scale and Inventory of Interpersonal Problems. Correlational and regression analyses were used to examine relations among study variables, including a hypothesized parallel mediation model. Results: Somatosensory amplification was significantly associated with attachment anxiety, but not attachment avoidance. Regression analyses, controlling for general anxiety symptoms and gender, found that interpersonal sensitivity (but not aggression or ambivalence) mediated the link between attachment anxiety and somatosensory amplification. Limitations: Study limitations include the use of cross-sectional data and a non-clinical sample. Conclusion: The findings indicate that somatosensory amplification may be related to individuals’ attachment anxiety, through the mediating effect of interpersonal sensitivity problems.

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Shinmura, Kazuya, Hisami Kato, Yuichi Kawanishi, Katsuhiro Yoshimura, Kazuo Tsuchiya, Yoshiyuki Takahara, Seiji Hosokawa, Akikazu Kawase, Kazuhito Funai, and Haruhiko Sugimura. "POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma." Cancers 11, no. 5 (May 24, 2019): 722. http://dx.doi.org/10.3390/cancers11050722.

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DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs). In the present study, we examined whether abnormal POLQ expression may be involved in the pathogenesis of lung adenocarcinoma (LAC). First, we found overexpression of POLQ at both the mRNA and protein levels in LAC, using data from the Cancer Genome Atlas (TCGA) database and by immunohistochemical analysis of our LAC series. POLQ overexpression was associated with an advanced pathologic stage and an increased total number of somatic mutations in LAC. When H1299 human lung cancer cell clones overexpressing POLQ were established and examined, the clones showed resistance to a DSB-inducing chemical in the clonogenic assay and an increased frequency of mutations in the supF forward mutation assay. Further analysis revealed that POLQ overexpression was also positively correlated with Polo Like Kinase 4 (PLK4) overexpression in LAC, and that PLK4 overexpression in the POLQ-overexpressing H1299 cells induced centrosome amplification. Finally, analysis of the TCGA data revealed that POLQ overexpression was associated with an increased somatic mutation load and PLK4 overexpression in diverse human cancers; on the other hand, overexpressions of nine TLS polymerases other than POLQ were associated with an increased somatic mutation load at a much lower frequency. Thus, POLQ overexpression is associated with advanced pathologic stage, increased somatic mutation load, and PLK4 overexpression, the last inducing centrosome amplification, in LAC, suggesting that POLQ overexpression is involved in the pathogenesis of LAC.

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Hunt, J. D., M. Valentine, and A. Tereba. "Excision of N-myc from chromosome 2 in human neuroblastoma cells containing amplified N-myc sequences." Molecular and Cellular Biology 10, no. 2 (February 1990): 823–29. http://dx.doi.org/10.1128/mcb.10.2.823.

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Amplification of one of three growth-stimulating myc genes is a common method by which many tumor types gain a proliferative advantage. In metastatic human neuroblastoma, the amplification of the N-myc locus, located on chromosome 2, is a dominant feature of this usually fatal pediatric cancer. Of the many models proposed to explain this amplification, all incorporate as the initial step either disproportionate overreplication of the chromosomal site or recombination across a loop structure. The original locus is retained within the chromosome in the overreplication models but is excised in the recombination models. To test these models, we have used somatic cell hybrids to separate and analyze the chromosomes 2 from a neuroblastoma cell line containing in vivo amplified N-myc. Our results demonstrate that N-myc is excised from one of the chromosomes, suggesting that deletion is a requisite part of gene amplification in a naturally occurring system.

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Hunt, J. D., M. Valentine, and A. Tereba. "Excision of N-myc from chromosome 2 in human neuroblastoma cells containing amplified N-myc sequences." Molecular and Cellular Biology 10, no. 2 (February 1990): 823–29. http://dx.doi.org/10.1128/mcb.10.2.823-829.1990.

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Amplification of one of three growth-stimulating myc genes is a common method by which many tumor types gain a proliferative advantage. In metastatic human neuroblastoma, the amplification of the N-myc locus, located on chromosome 2, is a dominant feature of this usually fatal pediatric cancer. Of the many models proposed to explain this amplification, all incorporate as the initial step either disproportionate overreplication of the chromosomal site or recombination across a loop structure. The original locus is retained within the chromosome in the overreplication models but is excised in the recombination models. To test these models, we have used somatic cell hybrids to separate and analyze the chromosomes 2 from a neuroblastoma cell line containing in vivo amplified N-myc. Our results demonstrate that N-myc is excised from one of the chromosomes, suggesting that deletion is a requisite part of gene amplification in a naturally occurring system.

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Muniswamy, Bychappa, Bharathi Kosaraju, Manoj Kumar Mishra, and Raghuramulu Yenugula. "Field Performance and Genetic Fidelity of Micropropagated Plants of Coffea canephora (Pierre ex A. Froehner)." Open Life Sciences 12, no. 1 (February 28, 2017): 1–11. http://dx.doi.org/10.1515/biol-2017-0001.

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AbstractThis study was conducted to compare the growth and yield of one of the commercial hybrid coffee cultivars (Coffea congensis x Coffea canephora) of robusta coffee established from somatic embryogenesis as well as conventional seedlings. Results indicated no statistically significant differences in the growth pattern or the cumulative yield between the somatic embryogenesis derived plants and the seedlings. The genetic fidelity of somatic embryogenesis derived plants and the mother plant was tested using sequence related amplified polymorphism (SRAP) markers. A total of 24 SRAP primers were employed for DNA analysis which produced a total of 153 clear, distinct and reproducible amplicons of variable size. Out of 24 SRAP primers, 9 primers produced amplification patterns which are identical between the mother plants and plants derived from somatic embryogenesis. Cluster analysis revealed more than 95% genetic similarity between the somatic embryogenesis derived plants and the mother plants indicating a high degree of genetic fidelity. The present study clearly demonstrates the usefulness of SRAP markers in genetic fidelity analysis of coffee.

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Ura, Hiroki, Sumihito Togi, and Yo Niida. "Dual Deep Sequencing Improves the Accuracy of Low-Frequency Somatic Mutation Detection in Cancer Gene Panel Testing." International Journal of Molecular Sciences 21, no. 10 (May 16, 2020): 3530. http://dx.doi.org/10.3390/ijms21103530.

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Cancer gene panel testing requires accurate detection of somatic mosaic mutations, as the test sample consists of a mixture of cancer cells and normal cells; each minor clone in the tumor also has different somatic mutations. Several studies have shown that the different types of software used for variant calling for next generation sequencing (NGS) can detect low-frequency somatic mutations. However, the accuracy of these somatic variant callers is unknown. We performed cancer gene panel testing in duplicate experiments using three different high-fidelity DNA polymerases in pre-capture amplification steps and analyzed by three different variant callers, Strelka2, Mutect2, and LoFreq. We selected six somatic variants that were detected in both experiments with more than two polymerases and by at least one variant caller. Among them, five single nucleotide variants were verified by CEL nuclease-mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining (CHIPS) and Sanger sequencing. In silico analysis indicated that the FBXW7 and MAP3K1 missense mutations cause damage at the protein level. Comparing three somatic variant callers, we found that Strelka2 detected more variants than Mutect2 and LoFreq. We conclude that dual sequencing with Strelka2 analysis is useful for detection of accurate somatic mutations in cancer gene panel testing.

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Rzeszutek, Iwona, Xyrus X. Maurer-Alcalá, and Mariusz Nowacki. "Programmed genome rearrangements in ciliates." Cellular and Molecular Life Sciences 77, no. 22 (May 27, 2020): 4615–29. http://dx.doi.org/10.1007/s00018-020-03555-2.

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Abstract Ciliates are a highly divergent group of unicellular eukaryotes with separate somatic and germline genomes found in distinct dimorphic nuclei. This characteristic feature is tightly linked to extremely laborious developmentally regulated genome rearrangements in the development of a new somatic genome/nuclei following sex. The transformation from germline to soma genome involves massive DNA elimination mediated by non-coding RNAs, chromosome fragmentation, as well as DNA amplification. In this review, we discuss the similarities and differences in the genome reorganization processes of the model ciliates Paramecium and Tetrahymena (class Oligohymenophorea), and the distantly related Euplotes, Stylonychia, and Oxytricha (class Spirotrichea).

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Daheim, Jacob, Shin Ye Kim, Ashley Neduvelil, and Nguyen P. Nguyen. "Men, Chronic Pain, and Prescription Pain Medication Use: The Role of Gender Role Beliefs in a Longitudinal Moderated Mediation Model." Pain Medicine 21, no. 12 (September 10, 2019): 3603–14. http://dx.doi.org/10.1093/pm/pnz200.

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Abstract Objective Although past research has established that men with chronic pain are more likely to misuse prescription pain medications in a myriad of ways compared with women, little is known about men’s medication use in the context of their gender role beliefs. The aim of the present study was to examine the role of men’s domestic gender role beliefs on their use of prescription pain medication for chronic pain. Methods Using a nationally representative data set with 304 men with chronic pain, this study examined a longitudinal moderated mediation model in which pain interference mediates the longitudinal relationship between somatic amplification and prescription pain medication use, with domestic gender role beliefs as a moderator of the aforementioned mediated relationship. Results Results indicated a significant moderated mediation model in which pain interference fully mediated the relationship between somatic amplification and prescription pain medication use, with men’s domestic gender role beliefs moderating this mediated relationship. Specifically, domestic gender role beliefs moderated the relationship between pain interference and prescription pain medication use. Men with higher levels of traditional domestic gender role beliefs strengthened the mediated relationship, contributing to increased prescription pain medication use. Conclusions These findings suggest that although men’s perceptions of somatic stimuli through its perceived interference contribute to their medication use, the extent to which they consume prescription pain medication depends on their beliefs in domestic gender roles during chronic pain.

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Journal articles on the topic 'Somatic amplification'

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