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; 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; Sabina Signoretti; Michael Seiler; Hsu Chao; Lihua Zou; The Cancer Genome Atlas Research Network

doi:10.1016/j.ccr.2014.07.014

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, Sabina Signoretti, Michael Seiler, Hsu Chao, Lihua Zou, The Cancer Genome Atlas Research Network

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

635 Scopus citations

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.

Original language	English (US)
Pages (from-to)	319-330
Number of pages	12
Journal	Cancer cell
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2014.07.014
State	Published - 2014

Funding

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).

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2014.07.014

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Davis, C. F., Ricketts, C. J., Wang, M., Yang, L., Cherniack, A. D., Shen, H., Buhay, C., Kang, H., Kim, S. C., Fahey, C. C., Hacker, K. E., Bhanot, G., Gordenin, D. A., Chu, A., Gunaratne, P. H., Biehl, M., Seth, S., Kaipparettu, B. A., Bristow, C. A., ... The Cancer Genome Atlas Research Network (2014). The somatic genomic landscape of chromophobe renal cell carcinoma. Cancer cell, 26(3), 319-330. https://doi.org/10.1016/j.ccr.2014.07.014

@article{d23eddb162884dc3bbc06b6ba850c35b,

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.",

author = "Davis, {Caleb F.} and Ricketts, {Christopher J.} and Min Wang and Lixing Yang and Cherniack, {Andrew D.} and Hui Shen and Christian Buhay and Hyojin Kang and Kim, {Sang Cheol} and Fahey, {Catherine C.} and Hacker, {Kathryn E.} and Gyan Bhanot and Gordenin, {Dmitry A.} and Andy Chu and Gunaratne, {Preethi H.} and Michael Biehl and Sahil Seth and Kaipparettu, {Benny A.} and Bristow, {Christopher A.} and Donehower, {Lawrence A.} and Wallen, {Eric M.} and Smith, {Angela B.} and Tickoo, {Satish K.} and Pheroze Tamboli and Victor Reuter and Schmidt, {Laura S.} and Hsieh, {James J.} and Choueiri, {Toni K.} and Hakimi, {A. Ari} and Lynda Chin and Matthew Meyerson and Raju Kucherlapati and Park, {Woong Yang} and Robertson, {A. Gordon} and Laird, {Peter W.} and Henske, {Elizabeth P.} and Kwiatkowski, {David J.} and Park, {Peter J.} and Margaret Morgan and Brian Shuch and Donna Muzny and Wheeler, {David A.} and Linehan, {W. Marston} and Gibbs, {Richard A.} and Rathmell, {W. Kimryn} and Creighton, {Chad J.} and Sabina Signoretti and Michael Seiler and Hsu Chao and Lihua Zou and {The Cancer Genome Atlas Research Network}",

note = "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: {\textcopyright} 2014 Elsevier Inc.",

year = "2014",

doi = "10.1016/j.ccr.2014.07.014",

language = "English (US)",

volume = "26",

pages = "319--330",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "3",

}

Davis, CF, Ricketts, CJ, Wang, M, Yang, L, Cherniack, AD, Shen, H, Buhay, C, Kang, H, Kim, SC, Fahey, CC, Hacker, KE, Bhanot, G, Gordenin, DA, Chu, A, Gunaratne, PH, Biehl, M, Seth, S, Kaipparettu, BA, Bristow, CA, Donehower, LA, Wallen, EM, Smith, AB, Tickoo, SK, Tamboli, P, Reuter, V, Schmidt, LS, Hsieh, JJ, Choueiri, TK, Hakimi, AA, Chin, L, Meyerson, M, Kucherlapati, R, Park, WY, Robertson, AG, Laird, PW, Henske, EP, Kwiatkowski, DJ, Park, PJ, Morgan, M, Shuch, B, Muzny, D, Wheeler, DA, Linehan, WM, Gibbs, RA, Rathmell, WK, Creighton, CJ, Signoretti, S, Seiler, M, Chao, H, Zou, L & The Cancer Genome Atlas Research Network 2014, 'The somatic genomic landscape of chromophobe renal cell carcinoma', Cancer cell, vol. 26, no. 3, pp. 319-330. https://doi.org/10.1016/j.ccr.2014.07.014

TY - JOUR

T1 - The somatic genomic landscape of chromophobe renal cell carcinoma

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 - Zou, Lihua

AU - The Cancer Genome Atlas Research Network

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

UR - http://www.scopus.com/inward/citedby.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 -

The somatic genomic landscape of chromophobe renal cell carcinoma

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UN SDGs

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