Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma

Fengju Chen, Yiqun Zhang, Yasin Şenbabaoğlu, Giovanni Ciriello, Lixing Yang, Ed Reznik, Brian Shuch, Goran Micevic, Guillermo De Velasco, Eve Shinbrot, Michael S. Noble, Yiling Lu, Kyle R. Covington, Liu Xi, Jennifer A. Drummond, Donna Muzny, Hyojin Kang, Junehawk Lee, Pheroze Tamboli, Victor Reuter & 20 others Carl Simon Shelley, Benny A. Kaipparettu, Donald P. Bottaro, Andrew K. Godwin, Richard A. Gibbs, Gad Getz, Raju Kucherlapati, Peter J. Park, Chris Sander, Elizabeth P. Henske, Jane H. Zhou, David J. Kwiatkowski, Thai H. Ho, Toni K. Choueiri, James J. Hsieh, Rehan Akbani, Gordon Mills, A. Ari Hakimi, David A. Wheeler, Chad J. Creighton

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression), we classified 894 renal cell carcinomas (RCCs) of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes. Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR) could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.

Original languageEnglish (US)
Pages (from-to)2476-2489
Number of pages14
JournalCell Reports
Volume14
Issue number10
DOIs
StatePublished - Mar 15 2016
Externally publishedYes

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T-cells
Taxonomies
Genomics
Phosphatidylinositol 3-Kinases
Renal Cell Carcinoma
Metabolism
Chromatin
Phosphotransferases
Fusion reactions
Genes
Cells
RNA
DNA
Proteins
Modifier Genes
Gene Fusion
Nephrons
Biomarkers
T-Lymphocytes
Survival

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chen, F., Zhang, Y., Şenbabaoğlu, Y., Ciriello, G., Yang, L., Reznik, E., ... Creighton, C. J. (2016). Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. Cell Reports, 14(10), 2476-2489. https://doi.org/10.1016/j.celrep.2016.02.024

Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. / Chen, Fengju; Zhang, Yiqun; Şenbabaoğlu, Yasin; Ciriello, Giovanni; Yang, Lixing; Reznik, Ed; Shuch, Brian; Micevic, Goran; De Velasco, Guillermo; Shinbrot, Eve; Noble, Michael S.; Lu, Yiling; Covington, Kyle R.; Xi, Liu; Drummond, Jennifer A.; Muzny, Donna; Kang, Hyojin; Lee, Junehawk; Tamboli, Pheroze; Reuter, Victor; Shelley, Carl Simon; Kaipparettu, Benny A.; Bottaro, Donald P.; Godwin, Andrew K.; Gibbs, Richard A.; Getz, Gad; Kucherlapati, Raju; Park, Peter J.; Sander, Chris; Henske, Elizabeth P.; Zhou, Jane H.; Kwiatkowski, David J.; Ho, Thai H.; Choueiri, Toni K.; Hsieh, James J.; Akbani, Rehan; Mills, Gordon; Hakimi, A. Ari; Wheeler, David A.; Creighton, Chad J.

In: Cell Reports, Vol. 14, No. 10, 15.03.2016, p. 2476-2489.

Research output: Contribution to journalArticle

Chen, F, Zhang, Y, Şenbabaoğlu, Y, Ciriello, G, Yang, L, Reznik, E, Shuch, B, Micevic, G, De Velasco, G, Shinbrot, E, Noble, MS, Lu, Y, Covington, KR, Xi, L, Drummond, JA, Muzny, D, Kang, H, Lee, J, Tamboli, P, Reuter, V, Shelley, CS, Kaipparettu, BA, Bottaro, DP, Godwin, AK, Gibbs, RA, Getz, G, Kucherlapati, R, Park, PJ, Sander, C, Henske, EP, Zhou, JH, Kwiatkowski, DJ, Ho, TH, Choueiri, TK, Hsieh, JJ, Akbani, R, Mills, G, Hakimi, AA, Wheeler, DA & Creighton, CJ 2016, 'Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma', Cell Reports, vol. 14, no. 10, pp. 2476-2489. https://doi.org/10.1016/j.celrep.2016.02.024
Chen F, Zhang Y, Şenbabaoğlu Y, Ciriello G, Yang L, Reznik E et al. Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. Cell Reports. 2016 Mar 15;14(10):2476-2489. https://doi.org/10.1016/j.celrep.2016.02.024
Chen, Fengju ; Zhang, Yiqun ; Şenbabaoğlu, Yasin ; Ciriello, Giovanni ; Yang, Lixing ; Reznik, Ed ; Shuch, Brian ; Micevic, Goran ; De Velasco, Guillermo ; Shinbrot, Eve ; Noble, Michael S. ; Lu, Yiling ; Covington, Kyle R. ; Xi, Liu ; Drummond, Jennifer A. ; Muzny, Donna ; Kang, Hyojin ; Lee, Junehawk ; Tamboli, Pheroze ; Reuter, Victor ; Shelley, Carl Simon ; Kaipparettu, Benny A. ; Bottaro, Donald P. ; Godwin, Andrew K. ; Gibbs, Richard A. ; Getz, Gad ; Kucherlapati, Raju ; Park, Peter J. ; Sander, Chris ; Henske, Elizabeth P. ; Zhou, Jane H. ; Kwiatkowski, David J. ; Ho, Thai H. ; Choueiri, Toni K. ; Hsieh, James J. ; Akbani, Rehan ; Mills, Gordon ; Hakimi, A. Ari ; Wheeler, David A. ; Creighton, Chad J. / Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. In: Cell Reports. 2016 ; Vol. 14, No. 10. pp. 2476-2489.
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abstract = "On the basis of multidimensional and comprehensive molecular characterization (including DNA methalylation and copy number, RNA, and protein expression), we classified 894 renal cell carcinomas (RCCs) of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences among clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with TFE3 gene fusion or chromatin modifier genes were present within a specific subtype and spanned multiple subtypes. Differences in patient survival and in alteration of specific pathways (including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR) could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.",
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AU - Yang, Lixing

AU - Reznik, Ed

AU - Shuch, Brian

AU - Micevic, Goran

AU - De Velasco, Guillermo

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AU - Noble, Michael S.

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AU - Bottaro, Donald P.

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AU - Gibbs, Richard A.

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AU - Sander, Chris

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AU - Zhou, Jane H.

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AU - Ho, Thai H.

AU - Choueiri, Toni K.

AU - Hsieh, James J.

AU - Akbani, Rehan

AU - Mills, Gordon

AU - Hakimi, A. Ari

AU - Wheeler, David A.

AU - Creighton, Chad J.

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