This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Reference
- Whole-Exome Sequencing Studies of Nonhereditary (Sporadic) Parathyroid Adenomas.
- Paper ID
- COSP29415
- Authors
- 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
PMID: 22855342 (view at PubMed or Europe PMC) - 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