Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

被引：1801

作者：

Aguirre, Andrew J.

Hruban, Ralph H.

Raphael, Benjamin J.

机构：

来源：

CANCER CELL | 2017年 / 32卷 / 02期

基金：

美国国家科学基金会;

关键词：

LONG NONCODING RNA; HNF1A-AS1 REGULATES PROLIFERATION; COPY-NUMBER ALTERATION; PHASE PROTEIN ARRAY; DNA METHYLATION; TUMOR-SUPPRESSOR; HEREDITARY PANCREATITIS; MUTATIONAL LANDSCAPE; SEQUENCING REVEALS; CANCER GENES;

D O I：

10.1016/j.ccell.2017.07.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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, TGFI3R2,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.

引用

页码：185 / +

页数：32

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