Title

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

Authors

Li Ding, Washington University in St. Louis
Matthew H. Bailey, Washington University in St. Louis
Eduard Porta-Pardo, Centro Nacional de Supercomputación
Vesteinn Thorsson, Institute for Systems Biology
Antonio Colaprico, Université libre de Bruxelles (ULB)
Denis Bertrand, A-Star, Genome Institute of Singapore
David L. Gibbs, Institute for Systems Biology
Amila Weerasinghe, Washington University in St. Louis
Kuan lin Huang, Washington University in St. Louis
Collin Tokheim, Johns Hopkins University
Isidro Cortés-Ciriano, Harvard Medical School
Reyka Jayasinghe, Washington University in St. Louis
Feng Chen, Washington University in St. Louis
Lihua Yu, H3 Biomedicine, Inc.
Sam Sun, Baylor College of Medicine
Catharina Olsen, Université libre de Bruxelles (ULB)
Jaegil Kim, Broad Institute
Alison M. Taylor, Broad Institute
Andrew D. Cherniack, Broad Institute
Rehan Akbani, University of Texas MD Anderson Cancer Center
Chayaporn Suphavilai, A-Star, Genome Institute of Singapore
Niranjan Nagarajan, A-Star, Genome Institute of Singapore
Joshua M. Stuart, University of California, Santa Cruz
Gordon B. Mills, University of Texas MD Anderson Cancer Center
Matthew A. Wyczalkowski, Washington University in St. Louis
Benjamin G. Vincent, The University of North Carolina at Chapel Hill
Carolyn M. Hutter, National Human Genome Research Institute (NHGRI)
Jean Claude Zenklusen, National Cancer Institute (NCI)
Katherine A. Hoadley, The University of North Carolina at Chapel Hill
Michael C. Wendl, Washington University in St. Louis
llya Shmulevich, Institute for Systems Biology
Alexander J. Lazar, University of Texas MD Anderson Cancer Center
David A. Wheeler, Baylor College of Medicine

Document Type

Journal Article

Publication Date

4-5-2018

Journal

Cell

Volume

173

Issue

2

DOI

10.1016/j.cell.2018.03.033

Keywords

cancer; cancer genomics; omics; oncogenic process; TCGA

Abstract

© 2018 The Authors 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.

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