GRCh38 · COSMIC v99


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Genomic profiling reveals mutational landscape in parathyroid carcinomas
Paper ID
Pandya C, Uzilov AV, Bellizzi J, Lau CY, Moe AS, Strahl M, Hamou W, Newman LC, Fink MY, Antipin Y, Yu W, Stevenson M, Cavaco BM, Teh BT, Thakker RV, Morreau H, Schadt EE, Sebra R, Li SD, Arnold A and Chen R
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
JCI insight, 2017;2(6):e92061
ISSN: 2379-3708
PMID: 28352668 (view at PubMed or Europe PMC)
Parathyroid carcinoma (PC) is an extremely rare malignancy lacking effective therapeutic intervention. We generated and analyzed whole-exome sequencing data from 17 patients to identify somatic and germline genetic alterations. A panel of selected genes was sequenced in a 7-tumor expansion cohort. We show that 47% (8 of 17) of the tumors harbor somatic mutations in the CDC73 tumor suppressor, with germline inactivating variants in 4 of the 8 patients. The PI3K/AKT/mTOR pathway was altered in 21% of the 24 cases, revealing a major oncogenic pathway in PC. We observed CCND1 amplification in 29% of the 17 patients, and a previously unreported recurrent mutation in putative kinase ADCK1. We identified the first sporadic PCs with somatic mutations in the Wnt canonical pathway, complementing previously described epigenetic mechanisms mediating Wnt activation. This is the largest genomic sequencing study of PC, and represents major progress toward a full molecular characterization of this rare malignancy to inform improved and individualized treatments.
Paper Status