The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

C. J. Ricketts; A. A. De Cubas; H. Fan; C. C. Smith; M. Lang; E. Reznik; R. Bowlby; E. A. Gibb; R. Akbani; R. Beroukhim; D. P. Bottaro; T. K. Choueiri; R. A. Gibbs; A. K. Godwin; S. Haake; A. A. Hakimi; E. P. Henske; J. J. Hsieh; T. H. Ho; R. S. Kanchi; B. Krishnan; D. J. Kwiatkowski; W. Lui; M. J. Merino; G. B. Mills; J. Myers; M. L. Nickerson; V. E. Reuter; L. S. Schmidt; C. S. Shelley; H. Shen; B. Shuch; S. Signoretti; R. Srinivasan; P. Tamboli; G. Thomas; B. G. Vincent; C. D. Vocke; D. A. Wheeler; L. Yang; W. Y. Kim; A. G. Robertson; Cancer Genome Atlas Research Network; P. T. Spellman; W. K. Rathmell; W. M. Linehan

doi:S2211-1247(18)30436-4 [pii]

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

C. J. Ricketts, A. A. De Cubas, H. Fan, C. C. Smith, M. Lang, E. Reznik, R. Bowlby, E. A. Gibb, R. Akbani, R. Beroukhim, D. P. Bottaro, T. K. Choueiri, R. A. Gibbs, A. K. Godwin, S. Haake, A. A. Hakimi, E. P. Henske, J. J. Hsieh, T. H. Ho, R. S. KanchiB. Krishnan, D. J. Kwiatkowski, W. Lui, M. J. Merino, G. B. Mills, J. Myers, M. L. Nickerson, V. E. Reuter, L. S. Schmidt, C. S. Shelley, H. Shen, B. Shuch, S. Signoretti, R. Srinivasan, P. Tamboli, G. Thomas, B. G. Vincent, C. D. Vocke, D. A. Wheeler, L. Yang, W. Y. Kim, A. G. Robertson, Cancer Genome Atlas Research Network, P. T. Spellman, W. K. Rathmell, W. M. Linehan

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

Abstract

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

Original language	English
Pages (from-to)	313-326.e5
Journal	Cell Reports
Volume	23
Issue number	1
DOIs	https://doi.org/S2211-1247(18)30436-4 [pii]
Publication status	Published - Apr 3 2018
Externally published	Yes

Keywords

CDKN2A
DNA hypermethylation
PanCanAtlas
TCGA
chromatin remodeling
chromophobe renal cell carcinoma
clear cell renal cell carcinoma
immune signature
papillary renal cell carcinoma

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Ricketts, C. J., Cubas, A. A. D., Fan, H., Smith, C. C., Lang, M., Reznik, E., Bowlby, R., Gibb, E. A., Akbani, R., Beroukhim, R., Bottaro, D. P., Choueiri, T. K., Gibbs, R. A., Godwin, A. K., Haake, S., Hakimi, A. A., Henske, E. P., Hsieh, J. J., Ho, T. H., ... Linehan, W. M. (2018). The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. Cell Reports, 23(1), 313-326.e5. https://doi.org/S2211-1247(18)30436-4 [pii]

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. / Ricketts, C. J.; Cubas, A. A. De; Fan, H.; Smith, C. C.; Lang, M.; Reznik, E.; Bowlby, R.; Gibb, E. A.; Akbani, R.; Beroukhim, R.; Bottaro, D. P.; Choueiri, T. K.; Gibbs, R. A.; Godwin, A. K.; Haake, S.; Hakimi, A. A.; Henske, E. P.; Hsieh, J. J.; Ho, T. H.; Kanchi, R. S.; Krishnan, B.; Kwiatkowski, D. J.; Lui, W.; Merino, M. J.; Mills, G. B.; Myers, J.; Nickerson, M. L.; Reuter, V. E.; Schmidt, L. S.; Shelley, C. S.; Shen, H.; Shuch, B.; Signoretti, S.; Srinivasan, R.; Tamboli, P.; Thomas, G.; Vincent, B. G.; Vocke, C. D.; Wheeler, D. A.; Yang, L.; Kim, W. Y.; Robertson, A. G.; Network, Cancer Genome Atlas Research; Spellman, P. T.; Rathmell, W. K.; Linehan, W. M.

In: Cell Reports, Vol. 23, No. 1, 03.04.2018, p. 313-326.e5.

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

Ricketts, CJ, Cubas, AAD, Fan, H, Smith, CC, Lang, M, Reznik, E, Bowlby, R, Gibb, EA, Akbani, R, Beroukhim, R, Bottaro, DP, Choueiri, TK, Gibbs, RA, Godwin, AK, Haake, S, Hakimi, AA, Henske, EP, Hsieh, JJ, Ho, TH, Kanchi, RS, Krishnan, B, Kwiatkowski, DJ, Lui, W, Merino, MJ, Mills, GB, Myers, J, Nickerson, ML, Reuter, VE, Schmidt, LS, Shelley, CS, Shen, H, Shuch, B, Signoretti, S, Srinivasan, R, Tamboli, P, Thomas, G, Vincent, BG, Vocke, CD, Wheeler, DA, Yang, L, Kim, WY, Robertson, AG, Network, CGAR, Spellman, PT, Rathmell, WK & Linehan, WM 2018, 'The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma', Cell Reports, vol. 23, no. 1, pp. 313-326.e5. https://doi.org/S2211-1247(18)30436-4 [pii]

Ricketts, C. J. ; Cubas, A. A. De ; Fan, H. ; Smith, C. C. ; Lang, M. ; Reznik, E. ; Bowlby, R. ; Gibb, E. A. ; Akbani, R. ; Beroukhim, R. ; Bottaro, D. P. ; Choueiri, T. K. ; Gibbs, R. A. ; Godwin, A. K. ; Haake, S. ; Hakimi, A. A. ; Henske, E. P. ; Hsieh, J. J. ; Ho, T. H. ; Kanchi, R. S. ; Krishnan, B. ; Kwiatkowski, D. J. ; Lui, W. ; Merino, M. J. ; Mills, G. B. ; Myers, J. ; Nickerson, M. L. ; Reuter, V. E. ; Schmidt, L. S. ; Shelley, C. S. ; Shen, H. ; Shuch, B. ; Signoretti, S. ; Srinivasan, R. ; Tamboli, P. ; Thomas, G. ; Vincent, B. G. ; Vocke, C. D. ; Wheeler, D. A. ; Yang, L. ; Kim, W. Y. ; Robertson, A. G. ; Network, Cancer Genome Atlas Research ; Spellman, P. T. ; Rathmell, W. K. ; Linehan, W. M. / The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma. In: Cell Reports. 2018 ; Vol. 23, No. 1. pp. 313-326.e5.

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abstract = "Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.",

keywords = "CDKN2A, DNA hypermethylation, PanCanAtlas, TCGA, chromatin remodeling, chromophobe renal cell carcinoma, clear cell renal cell carcinoma, immune signature, papillary renal cell carcinoma",

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T1 - The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

AU - Ricketts, C. J.

AU - Cubas, A. A. De

AU - Fan, H.

AU - Smith, C. C.

AU - Lang, M.

AU - Reznik, E.

AU - Bowlby, R.

AU - Gibb, E. A.

AU - Akbani, R.

AU - Beroukhim, R.

AU - Bottaro, D. P.

AU - Choueiri, T. K.

AU - Gibbs, R. A.

AU - Godwin, A. K.

AU - Haake, S.

AU - Hakimi, A. A.

AU - Henske, E. P.

AU - Hsieh, J. J.

AU - Ho, T. H.

AU - Kanchi, R. S.

AU - Krishnan, B.

AU - Kwiatkowski, D. J.

AU - Lui, W.

AU - Merino, M. J.

AU - Mills, G. B.

AU - Myers, J.

AU - Nickerson, M. L.

AU - Reuter, V. E.

AU - Schmidt, L. S.

AU - Shelley, C. S.

AU - Shen, H.

AU - Shuch, B.

AU - Signoretti, S.

AU - Srinivasan, R.

AU - Tamboli, P.

AU - Thomas, G.

AU - Vincent, B. G.

AU - Vocke, C. D.

AU - Wheeler, D. A.

AU - Yang, L.

AU - Kim, W. Y.

AU - Robertson, A. G.

AU - Network, Cancer Genome Atlas Research

AU - Spellman, P. T.

AU - Rathmell, W. K.

AU - Linehan, W. M.

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PY - 2018/4/3

Y1 - 2018/4/3

N2 - Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

AB - Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

KW - CDKN2A

KW - DNA hypermethylation

KW - PanCanAtlas

KW - TCGA

KW - chromatin remodeling

KW - chromophobe renal cell carcinoma

KW - clear cell renal cell carcinoma

KW - immune signature

KW - papillary renal cell carcinoma

U2 - S2211-1247(18)30436-4 [pii]

DO - S2211-1247(18)30436-4 [pii]

M3 - Article

VL - 23

SP - 313-326.e5

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

ER -