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Reference

Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas.

Paper Id
COSP29415
Authors
Newey PJ,Nesbit MA,Rimmer AJ,Attar M,Head RT,Christie PT,Gorvin CM,Stechman M,Gregory L,Mihai R,Sadler G,McVean G,Buck D and Thakker RV
Affiliation
Academic Endocrine Unit (P.J.N., M.A.N., R.T.H., P.T.C., C.M.G., M.S., R.V.T.), Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, United Kingdom; Bioinformatics and Statistical Genetics Group (A.J.R., G.M.) and High-Throughput Genomics Group (M.A., L.G., D.B.), Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; and Department of Surgery (M.S., R.M., G.S.), John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford OX3 9DU, United Kingdom.
Journal
The Journal of clinical endocrinology and metabolism 2012
ISSN:1945-7197
PUBMED:22855342
Abstract
Context:Genetic abnormalities, such as those of multiple endocrine neoplasia type 1 (MEN1) and Cyclin D1 (CCND1) genes, occur in <50% of nonhereditary (sporadic) parathyroid adenomas.Objective:To identify genetic abnormalities in nonhereditary parathyroid adenomas by whole-exome sequence analysis.Design:Whole-exome sequence analysis was performed on parathyroid adenomas and leukocyte DNA samples from 16 postmenopausal women without a family history of parathyroid tumors or MEN1 and in whom primary hyperparathyroidism due to single-gland disease was cured by surgery. Somatic variants confirmed in this discovery set were assessed in 24 other parathyroid adenomas.Results:Over 90% of targeted exons were captured and represented by more than 10 base reads. Analysis identified 212 somatic variants (median eight per tumor; range, 2-110), with the majority being heterozygous nonsynonymous single-nucleotide variants that predicted missense amino acid substitutions. Somatic MEN1 mutations occurred in six of 16 (∼35%) parathyroid adenomas, in association with loss of heterozygosity on chromosome 11. However, no other gene was mutated in more than one tumor. Mutations in several genes that may represent low-frequency driver mutations were identified, including a protection of telomeres 1 (POT1) mutation that resulted in exon skipping and disruption to the single-stranded DNA-binding domain, which may contribute to increased genomic instability and the observed high mutation rate in one tumor.Conclusions:Parathyroid adenomas typically harbor few somatic variants, consistent with their low proliferation rates. MEN1 mutation represents the major driver in sporadic parathyroid tumorigenesis although multiple low-frequency driver mutations likely account for tumors not harboring somatic MEN1 mutations.
Paper Status
Curated
Genes Analysed
257
Mutated Samples
16
Total No. of Samples
16
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Genes Samples CDS Mutation AA Mutation
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Non-Mutant Genes Gene Id (COSG)
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Non-Mutant Samples Sample Id (COSS)
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Sample Name Mutation Count
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Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq
This tab shows the gene expression and copy number variation data for this study. [more details]

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The table currently shows only high value (numeric) copy number data. Copy number segments are excluded if the total copy number and minor allele values are unknown.

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Sample Gene Expression Expr Level (Z-Score)

Over Expressed; Z-Score > 2.0

Under Expressed; Z-Score < -2.0

Normal; Z-Score within the range -2.0 to 2.0

CN Type Minor Allele Copy Number CN Segment Posn. Average Ploidy

1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy.

3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.

CNV
This tab shows the fusion mutations observed in this sample [more details]
Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type