Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Document Type

Journal Article

Publication Date

8-14-2017

Journal

Cancer Cell

Volume

32

Issue

2

DOI

10.1016/j.ccell.2017.07.007

Keywords

genomics; heterogeneity; KRAS; miRNA; molecular subtypes; pancreatic cancer; PDAC; RPPA; TCGA; tumor cellularity

Abstract

© 2017 Elsevier Inc. 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.

This document is currently not available here.

Share

COinS