The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

• DOI: 10.1016/j.ccr.2014.07.014
• Publication Date: 2014-08-21T12:09:19Z
• Authors: Caleb F. Davis; Christopher J. Ri...; Min Wang; Lixing Yang; Andrew D. Cherniack; Hui Shen; Christian Buhay; Hyojin Kang; Sang Cheol Kim; Catherine C. Fahey; Kathryn E. Hacker; Gyan Bhanot; Dmitry A. Gordenin; Andy Chu; Preethi H. Gunaratne; Michael Biehl; Sahil Seth; Benny A. Kaipparettu; Christopher A. Br...; Lawrence A. Doneh...; Eric M. Wallen; Angela B. Smith; Satish K. Tickoo; Pheroze Tamboli; Victor Reuter; Laura S. Schmidt; James J. Hsieh; Toni K. Choueiri; A. Ari Hakimi; Lynda Chin; Matthew Meyerson; Raju Kucherlapati; Woong-Yang Park; A. Gordon Robertson; Peter W. Laird; Elizabeth P. Henske; David J. Kwiatkowski; Peter J. Park; Margaret Morgan; Brian Shuch; Donna Muzny; David A. Wheeler; W. Marston Linehan; Richard A. Gibbs; W. Kimryn Rathmell; Chad J. Creighton; Chad J. Creighton; Caleb F. Davis; Margaret Morgan; Preethi H. Gunaratne; Lawrence A. Doneh...; Benny A. Kaipparettu; David A. Wheeler; Richard A. Gibbs; Sabina Signoretti; Andrew D. Cherniack; A. Gordon Robertson; Andy Chu; Toni K. Choueiri; Elizabeth P. Henske; David J. Kwiatkowski; Victor Reuter; James J. Hsieh; A. Ari Hakimi; Satish K. Tickoo; Christopher Ricketts; W. Marston Linehan; Laura S. Schmidt; Dmitry A. Gordenin; Gyan Bhanot; Michael Seiler; Pheroze Tamboli; W. Kimryn Rathmell; Catherine C. Fahey; Kathryn E. Hacker; Angela B. Smith; Eric M. Wallen; Hui Shen; Peter W. Laird; Brian Shuch; Donna Muzny; Christian Buhay; Min Wang; Hsu Chao; Mike Dahdouli; Liu Xi; Nipun Kakkar; Jeffrey G. Reid; Brittany Downs; Jennifer Drummond; Donna Morton; Harsha Doddapaneni; Lora Lewis; Adam English; Qingchang Meng; Christie Kovar; Qiaoyan Wang; Walker Hale; Alicia Hawes; Divya Kalra; Kimberly Walker; Bradley A. Murray; Carrie Sougnez; Gordon Saksena; Scott L. Carter; Steven E. Schumacher; Barbara Tabak; Travis I. Zack; Gad Getz; Rameen Beroukhim; Stacey B. Gabriel; Matthew Meyerson; Adrian Ally; Miruna Balasundaram; Inanc Birol; Denise Brooks; Yaron S.N. Butter...; Eric Chuah; Amanda Clarke; Noreen Dhalla; Ranabir Guin; Robert A. Holt; Katayoon Kasaian; Darlene Lee; Haiyan I. Li; Emilia Lim; Yussanne Ma; Michael Mayo; Richard A. Moore; Andrew J. Mungall; Jacqueline E. Schein; Payal Sipahimalani; Angela Tam; Nina Thiessen; Tina Wong; Steven J.M. Jones; Marco A. Marra; J. Todd Auman; Donghui Tan; Shaowu Meng; Corbin D. Jones; Katherine A. Hoadley; Piotr A. Mieczkowski; Lisle E. Mose; Stuart R. Jefferys; Jeffrey Roach; Umadevi Veluvolu; Matthew D. Wilkerson; Scot Waring; Elizabeth Buda; Junyuan Wu; Tom Bodenheimer; Alan P. Hoyle; Janae V. Simons; Mathew G. Soloway; Saianand Balu; Joel S. Parker; D. Neil Hayes; Charles M. Perou; Daniel J. Weisenb...; Moiz S. Bootwalla; Timothy Triche; Phillip H. Lai; David J. Van Den ...; Stephen B. Baylin; Fengju Chen; Cristian Coarfa; Michael S. Noble; Daniel DiCara; Hailei Zhang; Juok Cho; David I. Heiman; Nils Gehlenborg; Doug Voet; Pei Lin; Scott Frazer; Petar Stojanov; Yingchun Liu; Lihua Zou; Jaegil Kim; Michael S. Lawrence; Lynda Chin; Lixing Yang; Sahil Seth; Christopher A. Br...; Alexei Protopopov; Xingzhi Song; Jianhua Zhang; Angeliki Pantazi; Angela Hadjipanayis; Eunjung Lee; Lovelace J. Luquette; Semin Lee; Michael Parfenov; Netty Santoso; Jonathan Seidman; Andrew W. Xu; Raju Kucherlapati; Peter J. Park; Hyojin Kang; Junehawk Lee; Steven A. Roberts; Leszek J. Klimczak; David Fargo; Martin Lang; Yoon-La Choi; Sang Cheol Kim; June-Koo Lee; Woong-Yang Park; Wenyi Wang; Yu Fan; Jaeil Ahn; Rehan Akbani; John N. Weinstein; David Haussler; Singer Ma; Amie Radenbaugh; Jingchun Zhul; Michael Biehl; Tara M. Lichtenberg; Erik Zmuda; Aaron D. Black; Benjamin Hanf; Nilsa C. Ramirez; Lisa Wise; Jay Bowen; Kristen M. Leraas; Tracy M. Hall; Julie M. Gastier-...; William G. Kaelin; Leigh Thorne; Lori Boice; Mei Huang; Cathy Vocke; James Peterson; Robert Worrell; Maria Merino; Bogdan A. Czerniak; Kenneth D. Aldape; Christopher G. Wood; Paul T. Spellman; Michael B. Atkins; John Cheville; R. Houston Thompson; Mark A. Jensen; Todd Pihl; Yunhu Wan; Brenda Ayala; Julien Baboud; Sudhakar Velaga; Jessica Walton; Jia Liu; Sudha Chudamani; Ye Wu; Margi Sheth; Kenna R. Mills Shaw; John A. Demchok; Tanja Davidsen; Liming Yang; Zhining Wang; Roy W. Tarnuzzer; Jiashan Zhang; Greg Eley; Ina Felau; Jean Claude Zenkl...; Carolyn M. Hutter; Mark S. Guyer; Bradley A. Ozenbe...; Heidi J. Sofia
• Keywords: Chromophobe cell

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations.