Whole‐exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene

• DOI: 10.1002/gcc.22267
• Publication Date: 2015-05-29T20:08:57Z
• Authors: C. Christofer Juhlin; Adam Stenman; Felix Haglund; Victoria E. Clark; Taylor C. Brown; Jacob Baranoski; Kaya Bilguvar; Gerald Goh; Jenny Welander; Fredrika Svahn; Jill C. Rubinstein; Stefano Caramuta; Katsuhito Yasuno; Murat Günel; Martin Bäckdahl; Oliver Gimm; Peter Söderkvist; Manju L. Prasad; Reju Korah; Richard P. Lifton; Tobias Carling
• Keywords: Exome; HRAS

As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape PCCs identify novel gene candidates involved in disease development. A discovery cohort 15 wild type for mutations PCC susceptibility genes underwent whole‐exome sequencing, and an additional 83 served as verification targeted sequencing candidate mutations. low rate nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS EPAS1 were observed one case each, whereas remaining 13 cases did not exhibit established genes. SNVs aggregated apoptosis‐related pathways, COSMIC previously reported included ZAN , MITF WDTC1 CAMTA1 . Two somatic constitutional variant well‐established cancer lysine (K)‐specific methyltransferase 2D ( KMT2D MLL2 ) discovered sample prompting screening using focused exome‐sequencing cohort. An 11 displayed variants, which two recurrent. In total, missense found 14 (11 somatic, constitutional, undetermined) 99 (14%). Five functional FYR/SET domains KMT2D, constituting 36% all ‐mutated PCCs. expression upregulated compared normal adrenals, overexpression positively affected cell migration line. We conclude that represents recurrently mutated with potential implication © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.