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dc.contributor.authorFeigin, ME
dc.contributor.authorGarvin, T
dc.contributor.authorBailey, P
dc.contributor.authorWaddell, N
dc.contributor.authorChang, DK
dc.contributor.authorKelley, DR
dc.contributor.authorShuai, S
dc.contributor.authorGallinger, S
dc.contributor.authorMcPherson, JD
dc.contributor.authorGrimmond, SM
dc.contributor.authorKhurana, E
dc.contributor.authorStein, LD
dc.contributor.authorBiankin, AV
dc.contributor.authorSchatz, MC
dc.contributor.authorTuveson, DA
dc.date.accessioned2021-04-26T01:25:40Z
dc.date.available2021-04-26T01:25:40Z
dc.date.issued2017-06-01
dc.identifierpii: ng.3861
dc.identifier.citationFeigin, M. E., Garvin, T., Bailey, P., Waddell, N., Chang, D. K., Kelley, D. R., Shuai, S., Gallinger, S., McPherson, J. D., Grimmond, S. M., Khurana, E., Stein, L. D., Biankin, A. V., Schatz, M. C. & Tuveson, D. A. (2017). Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma. NATURE GENETICS, 49 (6), pp.825-+. https://doi.org/10.1038/ng.3861.
dc.identifier.issn1061-4036
dc.identifier.urihttp://hdl.handle.net/11343/269485
dc.description.abstractThe 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 effects of mutations on expression. We developed an expression modulation score that quantifies the strength of gene regulation imposed by each class of regulatory elements, and found the strongest elements were most frequently mutated, suggesting a selective advantage. Our detailed single-cancer analysis of noncoding alterations identifies regulatory mutations as candidates for diagnostic and prognostic markers, and suggests new mechanisms for tumor evolution.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleRecurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma
dc.typeJournal Article
dc.identifier.doi10.1038/ng.3861
melbourne.affiliation.departmentCentre for Cancer Research
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleNature Genetics
melbourne.source.volume49
melbourne.source.issue6
melbourne.source.pages825-+
melbourne.elementsid1207950
melbourne.openaccess.urlhttps://europepmc.org/articles/PMC5659388?pdf=render
melbourne.openaccess.statusPublished version
melbourne.contributor.authorGrimmond, Sean
dc.identifier.eissn1546-1718
melbourne.accessrightsAccess this item via the Open Access location


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