Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma Academic Article uri icon

Overview

MeSH Major

  • Carcinoma, Renal Cell
  • Genomics
  • Kidney Neoplasms

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.

authors

publication date

  • March 15, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4794376

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2016.02.024

PubMed ID

  • 26947078

Additional Document Info

start page

  • 2476

end page

  • 89

volume

  • 14

number

  • 10