title: The somatic genomic landscape of chromophobe renal cell carcinoma.
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.
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Caleb F
authors.initials: CF
authors.lastname: Davis
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, CRC Room 1W-5940, Bethesda, MD 20892, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ricketts
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lixing
authors.initials: L
authors.lastname: Yang
authors.affiliation: The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cherniack
authors.affiliation: USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Buhay
authors.affiliation: National Institute of Supercomputing and Networking, Korea Institute of Science and Technology Information, Daejeon, Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kang
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Sang Cheol
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Fahey
authors.affiliation: Curriculum in Genetics and Molecular Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hacker
authors.affiliation: 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.
authors.forename: Gyan
authors.initials: G
authors.lastname: Bhanot
authors.affiliation: National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Gordenin
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver BC V5Z 4S6, Canada.
authors.forename: Andy
authors.initials: A
authors.lastname: Chu
authors.affiliation: 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.
authors.forename: Preethi H
authors.initials: PH
authors.lastname: Gunaratne
authors.affiliation: Johann Bernoulli Institute for Mathematics and Computer Science, Intelligent Systems Group, University of Groningen, P.O. Box 407, 9700 AK Groningen, the Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Biehl
authors.affiliation: Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sahil
authors.initials: S
authors.lastname: Seth
authors.affiliation: 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.
authors.forename: Benny A
authors.initials: BA
authors.lastname: Kaipparettu
authors.affiliation: Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bristow
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
authors.affiliation: Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wallen
authors.affiliation: Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tickoo
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Reuter
authors.affiliation: 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.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Schmidt
authors.affiliation: 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.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.affiliation: 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.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.affiliation: 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.
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.affiliation: 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.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea; Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver BC V5Z 4S6, Canada.
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Robertson
authors.affiliation: USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.affiliation: 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.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Henske
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.affiliation: Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Department of Urology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Shuch
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Muzny
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, CRC Room 1W-5940, Bethesda, MD 20892, USA.
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: 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.
authors.forename: W Kimryn
authors.initials: WK
authors.lastname: Rathmell
authors.affiliation: 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.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D059472:Exome; D015894:Genome, Human; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics; D059467:Transcriptome
chemical_list: D004272:DNA, Mitochondrial; C509186:TERT protein, human; D019098:Telomerase