Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/17638
Title: Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies.
Authors: Colebatch, Andrew J;Di Stefano, Leon;Wong, Stephen Q;Hannan, Ross D;Waring, Paul M;Dobrovic, Alexander;McArthur, Grant A;Papenfuss, Anthony T
Affiliation: Research Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Victoria, Australia
Department of Pathology, University of Melbourne, Victoria, Australia
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Australian Capital Territory, Australia
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Victoria, Australia
School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia
Department of Medical Biology, University of Melbourne, Victoria, Australia
Issue Date: 11-Oct-2016
Citation: Oncotarget 2016; 7(41): 66569-66585
Abstract: Most 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17638
DOI: 10.18632/oncotarget.11892
PubMed URL: 27611953
Type: Journal Article
Subjects: gene promoter
melanoma
non-coding mutations
transcription factors
ultraviolet radiation
Appears in Collections:Journal articles

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