Genomic profiling reveals mutational landscape in parathyroid carcinomas

• DOI: 10.1172/jci.insight.92061
• Publication Date: 2017-03-22T15:01:42Z
• Authors: Chetanya Pandya; Andrew V. Uzilov; Justin Bellizzi; Chun Yee Lau; Aye S. Moe; Maya Strahl; Wissam Hamou; Leah C. Newman; Marc Y. Fink; Yevgeniy Antipin; Willie Yu; Mark Stevenson; Branca M. Cavaco; Bin T. Teh; Rajesh V. Thakker; Hans Morreau; Eric E. Schadt; Robert Sebra; Shuyu D. Li; Andrew Arnold; Rong Chen
• Keywords: Exome; MLH1

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 germline genetic alterations. A panel of selected genes was sequenced in a 7-tumor expansion cohort. show that 47% (8 17) the tumors harbor mutations CDC73 tumor suppressor, with inactivating variants 4 8 patients. The PI3K/AKT/mTOR pathway altered 21% 24 cases, revealing major oncogenic PC. observed CCND1 amplification 29% patients, previously unreported recurrent mutation putative kinase ADCK1. identified first sporadic PCs Wnt canonical pathway, complementing described epigenetic mechanisms mediating activation. This largest genomic study PC, represents progress toward full molecular characterization this inform improved individualized treatments.