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Integrated genomic characterization of pancreatic ductal adenocarcinoma


We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFbetaR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.

Type Journal
ISBN 1878-3686 (Electronic) 1535-6108 (Linking)
Authors Cancer Genome Atlas Research Network.
Responsible Garvan Author Amber Johns
Publisher Name CANCER CELL
Published Date 2017-08-14
Published Volume 32
Published Issue 2
Published Pages 185-203
Status Published in-print
DOI 10.1016/j.ccell.2017.07.007
URL link to publisher's version