Willie Yu1, John R McPherson, Mark Stevenson, Ronald van Eijk, Hong Lee Heng, Paul Newey, Anna Gan, Dina Ruano, Dachuan Huang, Song Ling Poon, Choon Kiat Ong, Tom van Wezel, Branca Cavaco, Steven G Rozen, Patrick Tan, Bin T Teh, Rajesh V Thakker, Hans Morreau. 1. Laboratory of Cancer Epigenome (W.Y., H.L.H., A.G., D.H., S.L.P., C.K.O., B.T.T.), Division of Medical Sciences, National Cancer Centre Singapore, 169610 Singapore; Division of Cancer and Stem Cell Biology (W.Y., J.R.M., H.L.H., D.H., S.L.P., C.K.O., S.G.R., P.T., B.T.T.), Duke-National University of Singapore Graduate Medical School, 169857 Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering (W.Y.), 117456 Singapore; Academic Endocrine Unit, Nuffield Department of Clinical Medicine (M.S., P.N., R.V.T.), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, OX3 7LJ Oxford, United Kingdom; Department of Pathology (R.v.E., D.R., T.v.W., H.M.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Molecular Endocrinology Group, Molecular Pathobiology Research Centre Unit (U.I.P.M.) (B.C.) of the Portuguese Institute of Oncology from Lisbon Francisco Gentil (IPOLFG) and Chronic Diseases Research Centre (CEDOC), Faculty of Medical Sciences (FCM), New University of Lisbon (UNL), 1099-023 Lisbon, Portugal; Genome Institute of Singapore (P.T.), 138672 Singapore; and Cancer Science Institute of Singapore (P.T., B.T.T.), National University of Singapore, 117599 Singapore.
Abstract
CONTEXT: Cell division cycle 73 (CDC73), encoding the protein parafibromin, is the most prevalent mutated gene in familial and sporadic parathyroid carcinoma (PC). OBJECTIVE: To identify additional genetic abnormalities in PCs. DESIGN: Whole-exome sequencing was performed using DNA from seven pairs of matched PCs and one triplet containing double primary tumor and normal leukocyte. Somatic variants were confirmed using Sanger sequencing and recurrently mutated genes were assessed in 13 additional PCs as well as 40 parathyroid adenomas (PA). RESULTS: PC had an average of 51 somatic variants/tumor (range 3-176) with approximately 58% of variants occurring as nonsynonymous single nucleotide variants. The importance of CDC73 in PC is reinforced with a remarkable preferential amplification of the mutant CDC73 allele. Furthermore, recurrent germ line and somatic mutations in prune homolog 2 [Drosophila] (PRUNE2) were found in PC and computationally predicted to be deleterious; in addition, recurrent mutations in kinase genes related to cell migration and invasion were found. PRUNE2 showed recurrent mutations in 18% (4/22) of PCs with additional screening in 40 PAs revealing only one rare missense polymorphism (Asp1677Asn). For the first time, the mutational signature associated with apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-catalyzed cytosine-to-uracil deamination is found in a subset of PC. CONCLUSION: This study outlines the genetic landscape of PC and attempts to characterize the mutational processes shaping the PC genome.
CONTEXT: Cell division cycle 73 (CDC73), encoding the protein parafibromin, is the most prevalent mutated gene in familial and sporadic parathyroid carcinoma (PC). OBJECTIVE: To identify additional genetic abnormalities in PCs. DESIGN: Whole-exome sequencing was performed using DNA from seven pairs of matched PCs and one triplet containing double primary tumor and normal leukocyte. Somatic variants were confirmed using Sanger sequencing and recurrently mutated genes were assessed in 13 additional PCs as well as 40 parathyroid adenomas (PA). RESULTS: PC had an average of 51 somatic variants/tumor (range 3-176) with approximately 58% of variants occurring as nonsynonymous single nucleotide variants. The importance of CDC73 in PC is reinforced with a remarkable preferential amplification of the mutant CDC73 allele. Furthermore, recurrent germ line and somatic mutations in prune homolog 2 [Drosophila] (PRUNE2) were found in PC and computationally predicted to be deleterious; in addition, recurrent mutations in kinase genes related to cell migration and invasion were found. PRUNE2 showed recurrent mutations in 18% (4/22) of PCs with additional screening in 40 PAs revealing only one rare missense polymorphism (Asp1677Asn). For the first time, the mutational signature associated with apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-catalyzed cytosine-to-uracil deamination is found in a subset of PC. CONCLUSION: This study outlines the genetic landscape of PC and attempts to characterize the mutational processes shaping the PC genome.
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 Journal: JCI Insight Date: 2017-03-23
Authors: Yulong Li; Jianhua Zhang; Poorni R Adikaram; James Welch; Bin Guan; Lee S Weinstein; Haobin Chen; William F Simonds Journal: Endocr Relat Cancer Date: 2020-09 Impact factor: 5.678
Authors: Julia C F Quintanilha; Jin Wang; Alexander B Sibley; Wei Xu; Osvaldo Espin-Garcia; Chen Jiang; Amy S Etheridge; Mark J Ratain; Heinz-Josef Lenz; Monica Bertagnolli; Hedy L Kindler; Maura N Dickler; Alan Venook; Geoffrey Liu; Kouros Owzar; Danyu Lin; Federico Innocenti Journal: Int J Cancer Date: 2021-10-05 Impact factor: 7.316