Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.

Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu, Cancer Genome Atlas Research Network
Cancer Cell. 2017 32 (2): 185-203.e13

PMID: 28810144 · PMCID: PMC5964983 · DOI:10.1016/j.ccell.2017.07.007

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.

Copyright © 2017 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Carcinoma, Pancreatic Ductal DNA Methylation Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Genomics Genomics Humans Mutation Pancreatic Neoplasms Proteome Proto-Oncogene Proteins p21(ras) Transcriptome

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