Cell Reports (Mar 2016)
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,
- 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 B. Mills,
- A. Ari Hakimi,
- David A. Wheeler,
- Chad J. Creighton
Affiliations
- Fengju Chen
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Yiqun Zhang
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Yasin Şenbabaoğlu
- Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Giovanni Ciriello
- Department of Computational Biology, University of Lausanne, 1015 Lausanne, Switzerland
- Lixing Yang
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
- Ed Reznik
- Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Brian Shuch
- Department of Urology, Yale School of Medicine, New Haven, CT 06520, USA
- Goran Micevic
- Department of Dermatology, Yale University, New Haven, CT 06510, USA
- Guillermo De Velasco
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
- Eve Shinbrot
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Michael S. Noble
- The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
- Yiling Lu
- Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- Kyle R. Covington
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Liu Xi
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Jennifer A. Drummond
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Donna Muzny
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Hyojin Kang
- Department of Convergence Technology Research, Korea Institute of Science and Technology Information (KAIST), Daejeon 305-806, Korea
- Junehawk Lee
- Department of Convergence Technology Research, Korea Institute of Science and Technology Information (KAIST), Daejeon 305-806, Korea
- Pheroze Tamboli
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Victor Reuter
- Department of Pathology, Memorial Sloan-Kettering Cancer, New York, NY 10065, USA
- Carl Simon Shelley
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA
- Benny A. Kaipparettu
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Donald P. Bottaro
- Urologic Oncology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
- Andrew K. Godwin
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
- Richard A. Gibbs
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Gad Getz
- The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
- Raju Kucherlapati
- Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
- Peter J. Park
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
- Chris Sander
- Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- Elizabeth P. Henske
- The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
- Jane H. Zhou
- Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA
- David J. Kwiatkowski
- The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
- Thai H. Ho
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ 85054, USA
- Toni K. Choueiri
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
- James J. Hsieh
- Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
- Rehan Akbani
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Gordon B. Mills
- Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- A. Ari Hakimi
- Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
- David A. Wheeler
- Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
- Chad J. Creighton
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- DOI
- https://doi.org/10.1016/j.celrep.2016.02.024
- Journal volume & issue
-
Vol. 14,
no. 10
pp. 2476 – 2489
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.
