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.
APA Citation
Raphael, B., Hruban, R., Aguirre, A., Moffitt, R., Yeh, J., Stewart, C., Robertson, A., Cherniack, A., Gupta, M., Getz, G., Gabriel, S., Meyerson, M., Cibulskis, C., Fei, S., Hinoue, T., Shen, H., Laird, P., Ling, S., Lu, Y., Mills, G., Akbani, R., Loher, P., Londin, E., Rigoutsos, I., Telonis, A., Gibb, E., Goldenberg, A., Mezlini, A., Hoadley, K., Collisson, E., Lander, E., Murray, B., & Hess, J. (2017). Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell, 32 (2). http://dx.doi.org/10.1016/j.ccell.2017.07.007