Journal article
Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma
ME Feigin, T Garvin, P Bailey, N Waddell, DK Chang, DR Kelley, S Shuai, S Gallinger, JD McPherson, SM Grimmond, E Khurana, LD Stein, AV Biankin, MC Schatz, DA Tuveson
Nature Genetics | NATURE PORTFOLIO | Published : 2017
DOI: 10.1038/ng.3861
Abstract
The contributions of coding mutations to tumorigenesis are relatively well known; however, little is known about somatic alterations in noncoding DNA. Here we describe GECCO (Genomic Enrichment Computational Clustering Operation) to analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas (PDAs) and identify commonly mutated regulatory regions. We find recurrent noncoding mutations to be enriched in PDA pathways, including axon guidance and cell adhesion, and newly identified processes, including transcription and homeobox genes. We identified mutations in protein binding sites correlating with differential expression of proximal genes and experimentally validated effec..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank the members of the Tuveson laboratory, C. Vakoc and A. Siepel for discussions. D.A.T. is a distinguished scholar of the Lustgarten Foundation and Director of the Lustgarten Foundation-designated Laboratory of Pancreatic Cancer Research. D.A.T. is also supported by the Cold Spring Harbor Laboratory Association, the V Foundation, PCUK and the David Rubinstein Center for Pancreatic Cancer Research at MSKCC. In addition, we are grateful for support from the following: the STARR Foundation (I7-A718 for D.A.T.), DOD (W81XWH-13-PRCRP-IA for D.A.T.), Louis Morin Charitable Trust (M.E.F.) and NIH (5P30CA45508-26, 5P50CA101955-07, 1U10CA180944-03, 5U01CA168409-5, 1R01CA188134-01A1 and 1R01CA190092-03 for D.A.T. and R01HG006677 for M.C.S.).