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 Donehower; 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; The Cancer Genome Atlas Research Network; 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

doi:10.1016/j.ccr.2014.07.014

The somatic genomic landscape of chromophobe renal cell carcinoma

Cancer Cell. 2014 Sep 8;26(3):319-330. doi: 10.1016/j.ccr.2014.07.014. Epub 2014 Aug 21.

Authors

Caleb F Davis¹, Christopher J Ricketts², Min Wang¹, Lixing Yang³, Andrew D Cherniack⁴, Hui Shen⁵, Christian Buhay¹, Hyojin Kang⁶, Sang Cheol Kim⁷, Catherine C Fahey⁸, Kathryn E Hacker⁸, Gyan Bhanot⁹, Dmitry A Gordenin¹⁰, Andy Chu¹¹, Preethi H Gunaratne¹², Michael Biehl¹³, Sahil Seth¹⁴, Benny A Kaipparettu¹⁵, Christopher A Bristow¹⁴, Lawrence A Donehower¹, Eric M Wallen¹⁶, Angela B Smith¹⁶, Satish K Tickoo¹⁷, Pheroze Tamboli¹⁸, Victor Reuter¹⁷, Laura S Schmidt¹⁹, James J Hsieh²⁰, Toni K Choueiri²¹, A Ari Hakimi²²; The Cancer Genome Atlas Research Network; Lynda Chin²³, Matthew Meyerson²⁴, Raju Kucherlapati²⁵, Woong-Yang Park²⁶, A Gordon Robertson¹¹, Peter W Laird⁵, Elizabeth P Henske²⁷, David J Kwiatkowski²⁷, Peter J Park²⁸, Margaret Morgan¹, Brian Shuch²⁹, Donna Muzny¹, David A Wheeler¹, W Marston Linehan², Richard A Gibbs¹, W Kimryn Rathmell³⁰, Chad J Creighton³¹

Collaborators

The Cancer Genome Atlas Research Network:
Chad J Creighton, Caleb F Davis, Margaret Morgan, Preethi H Gunaratne, Lawrence A Donehower, 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 Butterfield, 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 Weisenberger, Moiz S Bootwalla, Timothy Triche Jr, Phillip H Lai, David J Van Den Berg, 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 Bristow, 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-Foster, 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 Zenklusen, Carolyn M Hutter, Mark S Guyer, Bradley A Ozenberger, Heidi J Sofia

Affiliations

¹ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
² Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, CRC Room 1W-5940, Bethesda, MD 20892, USA.
³ Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
⁴ The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
⁵ USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA.
⁶ National Institute of Supercomputing and Networking, Korea Institute of Science and Technology Information, Daejeon, Korea.
⁷ Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
⁸ Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
⁹ Department of Molecular Biology and Biochemistry, Rutgers University, Busch Campus, Piscataway, NJ 08854, USA; Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
¹⁰ National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
¹¹ Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver BC V5Z 4S6, Canada.
¹² Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biology & Biochemistry, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA.
¹³ Johann Bernoulli Institute for Mathematics and Computer Science, Intelligent Systems Group, University of Groningen, P.O. Box 407, 9700 AK Groningen, the Netherlands.
¹⁴ Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁵ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁶ Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA.
¹⁷ Department of Pathology, Memorial Sloan-Kettering Cancer, 1275 York Avenue, New York, NY 10065, USA.
¹⁸ Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
¹⁹ Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, CRC Room 1W-5940, Bethesda, MD 20892, USA; Leidos Biomedical Research, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
²⁰ Department of Medicine, Weill-Cornell Medical College, New York, NY 10021, USA; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
²¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
²² Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
²³ The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
²⁴ The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
²⁵ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
²⁶ Samsung Genome Institute, Samsung Medical Center, Seoul, Korea; Sungkyunkwan University School of Medicine, Seoul, Korea.
²⁷ The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
²⁸ Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
²⁹ Department of Urology, Yale School of Medicine, New Haven, CT 06520, USA.
³⁰ Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Division of Hematology and Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. Electronic address: rathmell@med.unc.edu.
³¹ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: creighto@bcm.edu.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Carcinoma, Renal Cell / genetics*
Chromosome Breakpoints
Chromosome Deletion
Chromosomes, Human / genetics
DNA Copy Number Variations
DNA Methylation
DNA Mutational Analysis
DNA, Mitochondrial / genetics
Exome
Genome, Human
Humans
Kidney Neoplasms / genetics*
Molecular Sequence Data
Promoter Regions, Genetic
Telomerase / genetics
Transcriptome

Substances

DNA, Mitochondrial
TERT protein, human
Telomerase

Abstract

Publication types

MeSH terms

Substances

Grants and funding