The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

Caleb F Davis, Christopher J Ricketts, 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 Bristow, Lawrence A DonehowerEric 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, The Cancer Genome Atlas Research Network

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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.

Original languageEnglish
Pages (from-to)319-330
Number of pages12
JournalCancer cell
Issue number3
Publication statusPublished - 8-Sep-2014

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