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 ReuterCarl 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 B. Mills, A. Ari Hakimi, David A. Wheeler, Chad J. Creighton

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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.

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

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    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Chen, F., Zhang, Y., Şenbabaoğlu, Y., Ciriello, G., Yang, L., Reznik, E., Shuch, B., Micevic, G., De Velasco, G., Shinbrot, E., Noble, M. S., Lu, Y., Covington, K. R., Xi, L., Drummond, J. A., Muzny, D., Kang, H., Lee, J., Tamboli, P., ... 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