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Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
Ding, Li,Bailey, Matthew H.,Porta-Pardo, Eduard,Thorsson, Vesteinn,Colaprico, Antonio,Bertrand, Denis,Gibbs, David L.,Weerasinghe, Amila,Huang, Kuan-lin,Tokheim, Collin,Corté,s-Ciriano, Isidro,J Elsevier 2018 Cell Vol.173 No.2
<P><B>Summary</B></P> <P>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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An overview of PanCancer Atlas analyses on oncogenic molecular processes </LI> <LI> Germline genome affects somatic genomic landscape in a pathway-dependent fashion </LI> <LI> Genome mutations impact expression, signaling, and multi-omic profiles </LI> <LI> Mutation burdens and drivers influence immune-cell composition in microenvironment </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
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