Abstract

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing. A synthesized view on oncogenic processes based on PanCancer Atlas analyses highlights the complex impact of genome alterations on the signaling and multi-omic profiles of human cancers as well as their influence on tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)305-320.e10
JournalCell
Volume173
Issue number2
DOIs
StatePublished - Apr 5 2018

Keywords

  • TCGA
  • cancer
  • cancer genomics
  • omics
  • oncogenic process

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource
  • Functional Proteomics Reverse Phase Protein Array Core

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