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doi: 10.1371/journal.pone.0054742. Epub 2013 Jan 24.

Comprehensive analysis of DNA methylation in head and neck squamous cell carcinoma indicates differences by survival and clinicopathologic characteristics

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Comprehensive analysis of DNA methylation in head and neck squamous cell carcinoma indicates differences by survival and clinicopathologic characteristics

Justin A Colacino et al. PLoS One.2013.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the eighth most commonly diagnosed cancer in the United States. The risk of developing HNSCC increases with exposure to tobacco, alcohol and infection with human papilloma virus (HPV). HPV-associated HNSCCs have a distinct risk profile and improved prognosis compared to cancers associated with tobacco and alcohol exposure. Epigenetic changes are an important mechanism in carcinogenic progression, but how these changes differ between viral- and chemical-induced cancers remains unknown. CpG methylation at 1505 CpG sites across 807 genes in 68 well-annotated HNSCC tumor samples from the University of Michigan Head and Neck SPORE patient population were quantified using the Illumina Goldengate Methylation Cancer Panel. Unsupervised hierarchical clustering based on methylation identified 6 distinct tumor clusters, which significantly differed by age, HPV status, and three year survival. Weighted linear modeling was used to identify differentially methylated genes based on epidemiological characteristics. Consistent with previous in vitro findings by our group, methylation of sites in the CCNA1 promoter was found to be higher in HPV(+) tumors, which was validated in an additional sample set of 128 tumors. After adjusting for cancer site, stage, age, gender, alcohol consumption, and smoking status, HPV status was found to be a significant predictor for DNA methylation at an additional 11 genes, including CASP8 and SYBL1. These findings provide insight into the epigenetic regulation of viral vs. chemical carcinogenesis and could provide novel targets for development of individualized therapeutic and prevention regimens based on environmental exposures.

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Conflict of interest statement

Competing Interests:Laura S. Rozek was employed by Sequenom, but not at the time this manuscript was submitted. The Sequenom EpiTyper, a MALDI-TOF mass spectrometry based platform was used in this study. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. DNA methylation heatmap constructed using unsupervised hierarchical Ward clustering of the 711 CpG sites with the greatest variance across the 68 tumor samples identified six distinct methylation clusters.
Figure 2
Figure 2. Kaplan-Meier survival curves depicting three year survival for each of the six clusters identified via unsupervised hierarchical cluster analysis.
See this image and copyright information in PMC

References

    1. Marur S, Forastiere AA (2008) Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc 83: 489–501. - PubMed
    1. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, et al. (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356: 1944–1956. - PubMed
    1. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, et al. (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. Journal of the National Cancer Institute 92: 709–720. - PubMed
    1. Gillison ML, D’Souza G, Westra W, Sugar E, Xiao W, et al. (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100: 407–420. - PubMed
    1. Arthur AE, Duffy SA, Sanchez GI, Gruber SB, Terrell JE, et al. (2011) Higher Micronutrient Intake Is Associated With Human Papillomavirus-Positive Head and Neck Cancer: A Case-Only Analysis. Nutrition and cancer 63: 734–742. - PMC - PubMed

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