Multilevel genomics-based taxonomy of renal cell carcinoma Journal Article


Authors: 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.; Reuter, V.; Shelley, C. S.; Kaipparettu, B. A.; Bottaro, D. P.; Godwin, A. K.; Gibbs, R. A.; Getz, G.; Kucherlapati, R.; Park, P. J.; Sander, C.; Henske, E. P.; Zhou, J. H.; Kwiatkowski, D. J.; Ho, T. H.; Choueiri, T. K.; Hsieh, J. J.; Akbani, R.; Mills, G. B.; Hakimi, A. A.; Wheeler, D. A.; Creighton, C. J.
Article Title: Multilevel genomics-based taxonomy of renal cell carcinoma
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. © 2016 The Authors.
Journal Title: Cell Reports
Volume: 14
Issue: 10
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2016-03-15
Start Page: 2476
End Page: 2489
Language: English
DOI: 10.1016/j.celrep.2016.02.024
PROVIDER: scopus
PMCID: PMC4794376
PUBMED: 26947078
DOI/URL:
Notes: Article -- Export Date: 4 April 2016 -- Source: Scopus
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MSK Authors
  1. James J Hsieh
    125 Hsieh
  2. Chris Sander
    210 Sander
  3. Victor Reuter
    1224 Reuter
  4. Abraham Ari Hakimi
    323 Hakimi
  5. Eduard Reznik
    103 Reznik