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

The somatic genomic landscape of chromophobe renal cell carcinoma.

Collaborators (223)

Creighton CJ, Davis CF, Morgan M, Gunaratne PH, Donehower LA, Kaipparettu BA, Wheeler DA, Gibbs RA, Signoretti S, Cherniack AD, Robertson AG, Chu A, Choueiri TK, Henske EP, Kwiatkowski DJ, Reuter V, Hsieh JJ, Hakimi AA, Tickoo SK, Ricketts C, Linehan WM, Schmidt LS, Gordenin DA, Bhanot G, Seiler M, Tamboli P, Rathmell WK, Fahey CC, Hacker KE, Smith AB, Wallen EM, Shen H, Laird PW, Shuch B, Muzny D, Buhay C, Wang M, Chao H, Dahdouli M, Xi L, Kakkar N, Reid JG, Downs B, Drummond J, Morton D, Doddapaneni H, Lewis L, English A, Meng Q, Kovar C, Wang Q, Hale W, Hawes A, Kalra D, Walker K, Murray BA, Sougnez C, Saksena G, Carter SL, Schumacher SE, Tabak B, Zack TI, Getz G, Beroukhim R, Gabriel SB, Meyerson M, Ally A, Balasundaram M, Birol I, Brooks D, Butterfield YSN, Chuah E, Clarke A, Dhalla N, Guin R, Holt RA, Kasaian K, Lee D, Li HI, Lim E, Ma Y, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Thiessen N, Wong T, Jones SJM, Marra MA, Auman JT, Tan D, Meng S, Jones CD, Hoadley KA, Mieczkowski PA, Mose LE, Jefferys SR, Roach J, Veluvolu U, Wilkerson MD, Waring S, Buda E, Wu J, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Balu S, Parker JS, Hayes DN, Perou CM, Weisenberger DJ, Bootwalla MS, Triche T Jr, Lai PH, Van Den Berg DJ, Baylin SB, Chen F, Coarfa C, Noble MS, DiCara D, Zhang H, Cho J, Heiman DI, Gehlenborg N, Voet D, Lin P, Frazer S, Stojanov P, Liu Y, Zou L, Kim J, Lawrence MS, Chin L, Yang L, Seth S, Bristow CA, Protopopov A, Song X, Zhang J, Pantazi A, Hadjipanayis A, Lee E, Luquette LJ, Lee S, Parfenov M, Santoso N, Seidman J, Xu AW, Kucherlapati R, Park PJ, Kang H, Lee J, Roberts SA, Klimczak LJ, Fargo D, Lang M, Choi YL, Kim SC, Lee JK, Park WY, Wang W, Fan Y, Ahn J, Akbani R, Weinstein JN, Haussler D, Ma S, Radenbaugh A, Zhul J, Biehl M, Lichtenberg TM, Zmuda E, Black AD, Hanf B, Ramirez NC, Wise L, Bowen J, Leraas KM, Hall TM, Gastier-Foster JM, Kaelin WG, Thorne L, Boice L, Huang M, Vocke C, Peterson J, Worrell R, Merino M, Czerniak BA, Aldape KD, Wood CG, Spellman PT, Atkins MB, Cheville J, Thompson RH, Jensen MA, Pihl T, Wan Y, Ayala B, Baboud J, Velaga S, Walton J, Liu J, Chudamani S, Wu Y, Sheth M, Mills Shaw KR, Demchok JA, Davidsen T, Yang L, Wang Z, Tarnuzzer RW, Zhang J, Eley G, Felau I, Zenklusen JC, Hutter CM, Guyer MS, Ozenberger BA, Sofia HJ.

Author information

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.

PMID:
25155756
PMCID:
PMC4160352
DOI:
10.1016/j.ccr.2014.07.014
[Indexed for MEDLINE]
Free PMC Article

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