scholarly journals Amplification of theInsulin-Like Growth Factor 1 ReceptorGene Is a Rare Event in Adrenocortical Adenocarcinomas: Searching for Potential Mechanisms of Overexpression

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Tamaya Castro Ribeiro ◽  
Alexander Augusto Jorge ◽  
Madson Q. Almeida ◽  
Beatriz Marinho de Paula Mariani ◽  
Mirian Yumi Nishi ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Real Time ◽  
Real Time Pcr ◽  
Adrenocortical Carcinoma ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Prognostic Biomarker ◽  
Rare Event ◽  
Adrenocortical Tumors ◽  
Number Variation

Context.IGF1Roverexpression appears to be a prognostic biomarker of metastatic pediatric adrenocortical tumors. However, the molecular mechanisms that are implicated in its upregulation remain unknown.Aim. To investigate the potential mechanisms involved inIGF1Roverexpression.Patients and Methods. We studied 64 adrenocortical tumors.IGF1Rcopy number variation was determined in all patients using MLPA and confirmed using real time PCR. In a subgroup of 32 patients, automatic sequencing was used to identifyIGF1Rallelic variants and the expression of microRNAs involved inIGF1Rregulation by real time PCR.Results.IGF1Ramplification was detected in an adrenocortical carcinoma that was diagnosed in a 46-year-old woman with Cushing’s syndrome and virilization.IGF1Roverexpression was demonstrated in this case. In addition, gene amplification of otherlociwas identified in this adrenocortical malignant tumor, but noIGF1Rcopy number variation was evidenced in the remaining cases. Automatic sequencing revealed three known polymorphisms but they did not correlate with its expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not correlate withIGF1Rexpression.Conclusion. We demonstrated amplification and overexpression ofIGF1Rgene in only one adrenocortical carcinoma, suggesting that these combined events are uncommon. In addition,IGF1Rpolymorphisms and abnormal microRNA expression did not correlate withIGF1Rupregulation in adrenocortical tumors.

Diagnosing Smith–Magenis Syndrome and Duplication 17p11.2 Syndrome byRAI1Gene Copy Number Variation Using Quantitative Real-Time PCR

2008 ◽  
Vol 12 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Hoa T. Truong ◽  
Sara Solaymani-Kohal ◽  
Kevin R. Baker ◽  
Santhosh Girirajan ◽  
Stephen R. Williams ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Real Time ◽  
Real Time Pcr ◽  
Copy Number ◽  
Quantitative Real Time Pcr ◽  
Number Variation

scholarly journals Copy-Number Variation Genotyping of GSTT1 and GSTM1 Gene Deletions by Real-Time PCR

2009 ◽  
Vol 55 (9) ◽  
pp. 1680-1685 ◽  
Author(s):  
Matthew J Rose-Zerilli ◽  
Sheila J Barton ◽  
A John Henderson ◽  
Seif O Shaheen ◽  
John W Holloway
Keyword(s):  
Copy Number Variation ◽  
Real Time ◽  
Real Time Pcr ◽  
Copy Number ◽  
De Novo ◽  
Association Studies ◽  
Comparative Genome Hybridization ◽  
Glutathione S Transferase ◽  
Gene Deletions ◽  
Number Variation

Abstract Background: Structural variation in the human genome is increasingly recognized as being highly prevalent and having relevance to common human diseases. Array-based comparative genome-hybridization technology can be used to determine copy-number variation (CNV) across entire genomes, and quantitative PCR (qPCR) can be used to validate de novo variation or assays of common CNV in disease-association studies. Analysis of large qPCR data sets can be complicated and time-consuming, however. Methods: We describe qPCR assays for GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) gene deletions that can genotype up to 192 samples in duplicate 5-μL reaction volumes in <2 h on the ABI Prism 7900HT Sequence Detection System. To streamline data handling and analysis of these CNVs by qPCR, we developed a novel interactive, macro-driven Microsoft Excel® spreadsheet. As proof of principle, we used our software to analyze CNV data for 1478 DNA samples from a family-based cohort. Results: With only 8 ng of DNA template, we assigned CNV genotypes (i.e., 2, 1, or 0 copies) to either 96% (GSTM1) or 91% (GSTT1) of all DNA samples in a single round of PCR amplification. Genotyping accuracy, as ascertained by familial inheritance, was >99.5%, and independent genotype assignments with replicate real-time PCR runs were 100% concordant. Conclusions: The genotyping assay for GSTM1 and GSTT1 gene deletion is suitable for large genetic epidemiologic studies and is a highly effective analysis system that is readily adaptable to analysis of other CNVs. .

BIOM-34. GENOMIC PROFILING IDENTIFIED COPY NUMBER VARIATIONS OF CDK4/6 AS A NOVEL PROGNOSTIC BIOMARKER FOR THALAMIC GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi18-vi18
Author(s):  
Mingyao Lai ◽  
zhaoming Zhou ◽  
Hainan Li ◽  
Jiangfen Zhou ◽  
Juan Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Copy Number Variation ◽  
Copy Number ◽  
Prognostic Biomarker ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Occurrence Rate ◽  
Number Variation ◽  
Thalamic Glioma ◽  
Astrocyte Differentiation

Abstract BACKGROUND Thalamic glioma is a rare tumor, which is poorly understood in adults. The genetic variation of this tumor is still unknown. In this study, we investigated the mutation landscape of thalamic glioma and compared the clinical outcomes between different mutation situations in thalamic glioma. METHODS Next-generation sequencing targeting 425 cancer-relevant genes was performed with 34 thalamic glioma tissue samples. Gene mutations and copy number variations were investigated for prognostic effect with overall survival data. RESULTS Several diagnostic and prognostic biomarkers appeared in our thalamic glioma cohort, including TP53 (56%), EGFR (41%), TERT (35%), M CL1 (26%), PDGFRA (26%), PTEN (26%), CDK4/6 (24%), POLE (24%), PIK3CA (24%), NF1 (21%), ATR (21%), ATRX (18%), BRAF (15%), and ROS1 (12%). Among all genetic aberrations with a more than 10% occurrence rate, two mutations (TERT and PTEN) were associated with poor overall survival and one copy number variation (CDK4/6) was associated with favorable overall survival (univariate P < 0.1). Among these genes, CDK4/6 copy number variations (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.035–0.704; P = 0.016) remained significant survival associated in multivariate analyses. Copy number variations of CDK4/6 was seldom reported as a prognostic biomarker for glioma, especially for thalamic glioma in public databases. Besides, several gene mutations (BRIP1, MRE11A, MAP2K1, ROS1, MUTYH, JARID2, CTCF, and EGFR) were found positively associated with CDK4/6 copy number variations. Gene enrichment analysis demonstrated that those genes were related to astrocyte differentiation. CONCLUSIONS In our study, CDK4/6 copy number variation was determined as a favorable overall survival biomarker for thalamic glioma, and CDK4/6 copy number variation associated mutant genes were related to astrocyte differentiation, which could be the potential therapeutic targets for thalamic glioma.

Allelic Copy Number Variation inFSCN2Detected Using Allele-Specific Genotyping and Multiplex Real-Time PCRs

2008 ◽  
Vol 49 (9) ◽  
pp. 3799 ◽  
Author(s):  
Zi-Bing Jin ◽  
Michiko Mandai ◽  
Kohei Homma ◽  
Chie Ishigami ◽  
Yasuhiko Hirami ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Real Time ◽  
Copy Number ◽  
Number Variation ◽  
Allele Specific ◽  
Allelic Copy Number

scholarly journals Extreme copy number variation at a tRNA ligase affecting phenology and fitness in yellow monkeyflowers

2018 ◽  
Author(s):  
Thom Nelson ◽  
Patrick Monnahan ◽  
Mariah McIntosh ◽  
Findley R. Finseth ◽  
Kayli Anderson ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Wild Population ◽  
Intermediate Frequency ◽  
Single Copy ◽  
Multiple Traits ◽  
Fluctuating Selection ◽  
Mendelian Segregation ◽  
Number Variation

AbstractCopy number variation (CNV) is a major part of the genetic diversity segregating within populations, but remains poorly understood relative to single nucleotide variation. Here, we report on a tRNA ligase gene (Migut.N02091; RLG1a) exhibiting unprecedented, and fitness-relevant, CNV within an annual population of the yellow monkeyflower Mimulus guttatus. RLG1a variation was associated with multiple traits in pooled population sequencing (PoolSeq) scans of phenotypic and phenological cohorts. Resequencing of inbred lines revealed intermediate frequency three-copy variants of RLG1a (trip+; 5/35 = 14%), and trip+ lines exhibited elevated RLG1a expression under multiple conditions. trip+ carriers, in addition to being over-represented in late-flowering and large-flowered PoolSeq populations, flowered later under stressful conditions in a greenhouse experiment (P < 0.05). In wild population samples, we discovered an additional rare RLG1a variant (high+) that carries 250-300 copies of RLG1a totaling ∼5.7Mb (20-40% of a chromosome). In the progeny of a high+ carrier, Mendelian segregation of diagnostic alleles and qPCR-based copy counts indicate that high+ is a single tandem array unlinked from the single copy RLG1a locus. In the wild, high+ carriers had highest fitness in two particularly dry and/or hot years (2015 and 2017; both p < 0.01), while single copy individuals were twice as fecund as either CNV type in a lush year (2016: p < 0.005). Our results demonstrate fluctuating selection on CNVs affecting phenological traits in a wild population, suggest that plant tRNA ligases mediate stress-responsive life-history traits, and introduce a novel system for investigating the molecular mechanisms of gene amplification.

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