The somatic genomic landscape of chromophobe renal cell carcinoma.

C Davis,Christopher J Ricketts,Min Wang,Andrew D Cherniack,Hui Shen,Christian J Buhay,Hyojin Kang,S C 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 Bristow,Lawrence A Donehower,Eric M Wallen,Angela Smith,Satish K Tickoo,Pheroze Tamboli,Victor E Reuter,Laura S Schmidt,James J Hsieh,Toni K Choueiri,A Ari Hakimi,Lynda Chin,Matthew Meyerson,Raju Kucherlapati,W Park,A Gordon Robertson,Peter W Laird,Elizabeth Petri Henske,David J Kwiatkowski,Peter J Park,M Morgan,Brian Shuch,Donna M Muzny,David A Wheeler,W Marston Linehan,Richard A Gibbs,W Kimryn Rathmell,Chad J Creighton,Sabina Signoretti,Michael Seiler,Hsu Chao,Mike Dahdouli,Liu Xi,Nipun Kakkar,J G Reid, Brittany Downs,Jennifer Drummond,Donna Morton,Harsha Doddapaneni,Lora Lewis,Adam C English,Qingchang Meng,Christie L Kovar,Qiaoyan Wang, W H 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,Adrian Ally,Miruna Balasundaram,Inanc Birol,Denise Brooks,Yaron S N Butterfield,Eric Chuah, A F Clarke,Noreen Dhalla, Ranabir Guin,Robert A Holt,Katayoon Kasaian,Darlene Lee,Haiyan I Li,E Lim,Yussanne Ma,M A Mayo,R 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 Weisenberger,Moiz S Bootwalla,Timothy J Triche, Phillip H Lai,David J Van Den Berg,Stephen B Baylin,Fengju Chen,Cristian Coarfa,Michael S Noble,Daniel Dicara,Hailei Zhang, J Cho,D Heiman,Nils Gehlenborg, Doug Voet,Pei Lin,Scott Frazer,Petar Stojanov,Yingchun Liu,Lihua Zou,Jaegil Kim, Michael S Lawrence,Alexei Protopopov,X Song,Angeliki Pantazi,Angela Hadjipanayis,Eunjung Lee,Lovelace J Luquette,S Lee,Michael Parfenov,Netty Santoso,J G Seidman,Andrew W Xu,Steven A Roberts,Leszek J Klimczak,David C Fargo,Martin Lang,Yoonla Choi,Junekoo Lee,Wenyi Wang,Yu Fan,Jaeil Ahn,Rehan Akbani,John N Weinstein,David Haussler,S Ma,Amie Radenbaugh, Jingchun Zhul,Tara M Lichtenberg, Erik Zmuda,Aaron D Black,Benjamin Hanf,Nilsa C Ramirez,Lisa Wise,Jay Bowen,Kristen M Leraas, T Hall,Julie M Gastierfoster,William G Kaelin,Leigh B Thorne,Lori Boice,Mei Huang,Cathy D Vocke,James T Peterson, R Worrell,Maria J Merino,Bogdan Czerniak,Kenneth D Aldape,Christopher G Wood,Paul T Spellman,Michael B Atkins,John C Cheville,R Houston Thompson,Mark A Jensen,Todd D Pihl, Y Wan, Brenda Ayala,Julien Baboud, Sudhakar Velaga,J Walton,Jia Liu, Sudha Chudamani,Ye Wu,Margi Sheth,Kenna R Mills Shaw, John A Demchok,Tanja Davidsen,Liming Yang,Zhining Wang,Roy Tarnuzzer,Jiashan Zhang,Greg Eley,Ina Felau,Jean Claude Zenklusen,Carolyn M Hutter,Mark S Guyer,Bradley A Ozenberger,Heidi J Sofia

Cancer Cell（2014）

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摘要

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with 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 upregulation in cancer distinct from previously observed amplifications and point mutations.

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关键词

somatic genomic landscape,carcinoma

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