Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma
- PMID: 28810144
- PMCID: PMC5964983
- DOI: 10.1016/j.ccell.2017.07.007
Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma
Abstract
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, TGFβR2, 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.
Keywords: KRAS; PDAC; RPPA; TCGA; genomics; heterogeneity; miRNA; molecular subtypes; pancreatic cancer; tumor cellularity.
Copyright © 2017 Elsevier Inc. All rights reserved.
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References
-
- Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47–52. - PubMed
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