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Medline ® Abstract for Reference 4

of 'Molecular pathogenesis of exocrine pancreatic cancer'

4
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Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.
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Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu, Cancer Genome Atlas Research Network
SO
Cancer Cell. 2017;32(2):185.
 
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.
AD
PMID