Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/17638
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dc.contributor.authorColebatch, Andrew J-
dc.contributor.authorDi Stefano, Leon-
dc.contributor.authorWong, Stephen Q-
dc.contributor.authorHannan, Ross D-
dc.contributor.authorWaring, Paul M-
dc.contributor.authorDobrovic, Alexander-
dc.contributor.authorMcArthur, Grant A-
dc.contributor.authorPapenfuss, Anthony T-
dc.date.accessioned2018-05-02T23:36:37Z-
dc.date.available2018-05-02T23:36:37Z-
dc.date.issued2016-10-11-
dc.identifier.citationOncotarget 2016; 7(41): 66569-66585-
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/17638-
dc.description.abstractMost cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-related mutations. Although attention is increasingly being paid to mutations in non-coding regions, standard approaches to identifying significant mutations may not be appropriate and there has been limited analysis of mutational clusters in functionally annotated non-coding regions. We sought to identify clustered somatic mutations (hotspot regions across samples) in functionally annotated regions in melanoma and other cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma). Sliding window analyses revealed numerous recurrent clustered hotspot mutations in proximal promoters, with some specific clusters present in up to 25% of cases. Mutations in melanoma were clustered within ETS and Sp1 transcription factor binding motifs, had a UV signature and were identified in other cutaneous malignancies. Clinicopathologic correlation and mutation analysis support a causal role for chronic UV irradiation generating somatic mutations in transcription factor binding motifs of proximal promoters.-
dc.language.isoeng-
dc.subjectgene promoter-
dc.subjectMelanoma-
dc.subjectnon-coding mutations-
dc.subjecttranscription factors-
dc.subjectultraviolet radiation-
dc.titleClustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies.-
dc.typeJournal Article-
dc.identifier.journaltitleOncotarget-
dc.identifier.affiliationResearch Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Victoria, Australia-
dc.identifier.affiliationDepartment of Pathology, University of Melbourne, Victoria, Australia-
dc.identifier.affiliationBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia-
dc.identifier.affiliationACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Australian Capital Territory, Australia-
dc.identifier.affiliationTranslational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Victoria, Australia-
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia-
dc.identifier.affiliationSir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia-
dc.identifier.affiliationDepartment of Medical Biology, University of Melbourne, Victoria, Australia-
dc.identifier.doi10.18632/oncotarget.11892-
dc.identifier.pubmedid27611953-
dc.type.austinJournal Article-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeJournal Article-
item.languageiso639-1en-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptSurgery (University of Melbourne)-
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