TY - JOUR
T1 - The somatic genomic landscape of chromophobe renal cell carcinoma
AU - The Cancer Genome Atlas Research Network
AU - Davis, Caleb F.
AU - Ricketts, Christopher J.
AU - Wang, Min
AU - Yang, Lixing
AU - Cherniack, Andrew D.
AU - Shen, Hui
AU - Buhay, Christian
AU - Kang, Hyojin
AU - Kim, Sang Cheol
AU - Fahey, Catherine C.
AU - Hacker, Kathryn E.
AU - Bhanot, Gyan
AU - Gordenin, Dmitry A.
AU - Chu, Andy
AU - Gunaratne, Preethi H.
AU - Biehl, Michael
AU - Seth, Sahil
AU - Kaipparettu, Benny A.
AU - Bristow, Christopher A.
AU - Donehower, Lawrence A.
AU - Wallen, Eric M.
AU - Smith, Angela B.
AU - Tickoo, Satish K.
AU - Tamboli, Pheroze
AU - Reuter, Victor
AU - Schmidt, Laura S.
AU - Hsieh, James J.
AU - Choueiri, Toni K.
AU - Hakimi, A. Ari
AU - Chin, Lynda
AU - Meyerson, Matthew
AU - Kucherlapati, Raju
AU - Park, Woong Yang
AU - Robertson, A. Gordon
AU - Laird, Peter W.
AU - Henske, Elizabeth P.
AU - Kwiatkowski, David J.
AU - Park, Peter J.
AU - Morgan, Margaret
AU - Shuch, Brian
AU - Muzny, Donna
AU - Wheeler, David A.
AU - Linehan, W. Marston
AU - Gibbs, Richard A.
AU - Rathmell, W. Kimryn
AU - Creighton, Chad J.
AU - Signoretti, Sabina
AU - Seiler, Michael
AU - Chao, Hsu
AU - Dahdouli, Mike
N1 - Funding Information:
We wish to thank all patients and families who contributed to this study. This work was supported by the following grants from the NIH: 5U24CA143843 (D.A.W.), U54HG003273 (R.A.G.), 5U24CA143866 (M.A. Marra), KL2TR001109 and UL1TR001111 (A.B.S.), 5P50CA101942 (S. Signoretti), 5P50CA101942 (T.K.C.), U54 HG003067 (E. Lander); K24CA172355 (W.K.R.), Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (W.M.L., L.S.S., C.J.R., M.J. Merino), with federal funds from the Frederick National Lab, NIH, under contract HHSN261200800001E (L.S.S.), Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (D.A.G., S.A. Roberts, L.J. Klimczak, D. Fargo), and a training fellowship from the Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia (Grant No. T15 LM007093 to C.F.D.). Other grant support includes the J. Randall & Kathleen L. MacDonald Kidney Cancer Research Fund, the Tuttle Family Kidney Cancer Research Fund (J.J.H.), the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C2096 to W.-Y.P.), and the Korea Institute of Science and Technology Information (K-14-L01-C02-S04 and KSC-2013-C3-037) (for supercomputing resources including technical support).
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84908695210&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2014.07.014
DO - 10.1016/j.ccr.2014.07.014
M3 - Article
C2 - 25155756
AN - SCOPUS:84908695210
SN - 1535-6108
VL - 26
SP - 319
EP - 330
JO - Cancer Cell
JF - Cancer Cell
IS - 3
ER -