| Literature DB >> 26947078 |
Fengju Chen1, Yiqun Zhang1, Yasin Şenbabaoğlu2, Giovanni Ciriello3, Lixing Yang4, Ed Reznik2, Brian Shuch5, Goran Micevic6, Guillermo De Velasco7, Eve Shinbrot8, Michael S Noble9, Yiling Lu10, Kyle R Covington8, Liu Xi8, Jennifer A Drummond8, Donna Muzny8, Hyojin Kang11, Junehawk Lee12, Pheroze Tamboli13, Victor Reuter14, Carl Simon Shelley15, Benny A Kaipparettu16, Donald P Bottaro17, Andrew K Godwin18, Richard A Gibbs19, Gad Getz20, Raju Kucherlapati21, Peter J Park4, Chris Sander2, Elizabeth P Henske22, Jane H Zhou23, David J Kwiatkowski22, Thai H Ho24, Toni K Choueiri7, James J Hsieh25, Rehan Akbani26, Gordon B Mills10, A Ari Hakimi27, David A Wheeler19, Chad J Creighton28.
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.Entities:
Mesh：
Substances：
Year: 2016 PMID： 26947078 PMCID： PMC4794376 DOI： 10.1016/j.celrep.2016.02.024
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423