Genetic and Epigenetic Somatic Alterations in Head and Neck Squamous Cell Carcinomas Are Globally Coordinated but Not Locally Targeted

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dc.contributor.author Poage, Graham M. en_US
dc.contributor.author Christensen, Brock C. en_US
dc.contributor.author Houseman, E. Andres en_US
dc.contributor.author McClean, Michael D. en_US
dc.contributor.author Wiencke, John K. en_US
dc.contributor.author Posner, Marshall R. en_US
dc.contributor.author Clark, John R. en_US
dc.contributor.author Nelson, Heather H. en_US
dc.contributor.author Marsit, Carmen J. en_US
dc.contributor.author Kelsey, Karl T. en_US
dc.date.accessioned 2012-01-12T16:41:38Z
dc.date.available 2012-01-12T16:41:38Z
dc.date.issued 2010-3-11 en_US
dc.identifier.citation Poage, Graham M., Brock C. Christensen, E. Andres Houseman, Michael D. McClean, John K. Wiencke, Marshall R. Posner, John R. Clark, Heather H. Nelson, Carmen J. Marsit, Karl T. Kelsey. "Genetic and Epigenetic Somatic Alterations in Head and Neck Squamous Cell Carcinomas Are Globally Coordinated but Not Locally Targeted" PLoS ONE 5(3): e9651. (2010) en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/2144/3359
dc.description.abstract BACKGROUND. Solid tumors, including head and neck squamous cell carcinomas (HNSCC), arise as a result of genetic and epigenetic alterations in a sustained stress environment. Little work has been done that simultaneously examines the spectrum of both types of changes in human tumors on a genome-wide scale and results so far have been limited and mixed. Since it has been hypothesized that epigenetic alterations may act by providing the second carcinogenic hit in gene silencing, we sought to identify genome-wide DNA copy number alterations and CpG dinucleotide methylation events and examine the global/local relationships between these types of alterations in HNSCC. METHODOLOGY/PRINCIPAL FINDINGS. We have extended a prior analysis of 1,413 cancer-associated loci for epigenetic changes in HNSCC by integrating DNA copy number alterations, measured at 500,000 polymorphic loci, in a case series of 19 primary HNSCC tumors. We have previously demonstrated that local copy number does not bias methylation measurements in this array platform. Importantly, we found that the global pattern of copy number alterations in these tumors was significantly associated with tumor methylation profiles (p<0.002). However at the local level, gene promoter regions did not exhibit a correlation between copy number and methylation (lowest q=0.3), and the spectrum of genes affected by each type of alteration was unique. CONCLUSION/SIGNIFICANCE. This work, using a novel and robust statistical approach demonstrates that, although a "second hit" mechanism is not likely the predominant mode of action for epigenetic dysregulation in cancer, the patterns of methylation events are associated with the patterns of allele loss. Our work further highlights the utility of integrative genomics approaches in exploring the driving somatic alterations in solid tumors. en_US
dc.description.sponsorship Flight Attendant Medical Research Institute; National Institutes of Health (5R01CA078609-10, 2R01CA100679-06A1, 5RO1ES006717-13) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights Poage et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.title Genetic and Epigenetic Somatic Alterations in Head and Neck Squamous Cell Carcinomas Are Globally Coordinated but Not Locally Targeted en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0009651 en_US
dc.identifier.pubmedid 20300172 en_US
dc.identifier.pmcid 2836370 en_US

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