2015.02.16_Supplementary Figures_OPL methylation manuscript from New DNA Methylation Markers and Global DNA Hypomethylation Are Associated with Oral Cancer Development

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posted on 2023-04-03, 19:25 authored by Jean-Philippe Foy, Curtis R. Pickering, Vassiliki A. Papadimitrakopoulou, Jaroslav Jelinek, Steven H. Lin, William N. William, Mitchell J. Frederick, Jing Wang, Wenhua Lang, Lei Feng, Li Zhang, Edward S. Kim, You H. Fan, Waun K. Hong, Adel K. El-Naggar, J. Jack Lee, Jeffrey N. Myers, Jean-Pierre Issa, Scott M. Lippman, Li Mao, Pierre Saintigny

Supplementary Figure 1: Flow-chart describing the selection of 86 candidate genes. Supplementary Figure 2: Promoter methylation of 62/86 candidate genes in head and neck cancer, normal mucosa and blood. Supplementary Figure 3: Promoter methylation of 13/86 candidate genes in normal tissues. Supplementary Fig. 4: Hierarchical clustering of paired normal, dysplastic lesions and carcinomas (in situ or invasive) collected from 10 patients (3), using methylation profiles of 60/86 of our candidate genes. Supplementary Figure 5: (A) Hierarchical cluster analysis of oral squamous cell carcinoma and oral normal mucosa using candidate genes expression profiles. Supplementary Figure 6: Correlation of the percentage methylation of AGTR1.

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ARTICLE ABSTRACT

DNA promoter methylation of tumor suppressor genes and global DNA hypomethylation are common features of head and neck cancers. Our goal was to identify early DNA methylation changes in oral premalignant lesions (OPL) that may serve as predictive markers of developing oral squamous cell carcinoma (OSCC). Using high-throughput DNA methylation profiles of 24 OPLs, we found that the top 86 genes differentially methylated between patients who did or did not develop OSCC were simultaneously hypermethylated, suggesting that a CpG island methylation phenotype may occur early during OSCC development. The vast majority of the 86 genes were nonmethylated in normal tissues and hypermethylated in OSCC versus normal mucosa. We used pyrosequencing in a validation cohort of 44 patients to evaluate the degree of methylation of AGTR1, FOXI2, and PENK promoters CpG sites that were included in the top 86 genes and of LINE1 repetitive element methylation, a surrogate of global DNA methylation. A methylation index was developed by averaging the percent methylation of AGTR1, FOXI2, and PENK promoters; patients with a high methylation index had a worse oral cancer–free survival (P = 0.0030). On the other hand, patients with low levels of LINE1 methylation had a significantly worse oral cancer–free survival (P = 0.0153). In conclusion, AGTR1, FOXI2, and PENK promoter methylation and LINE1 hypomethylation may be associated with an increased risk of OSCC development in patients with OPLs. Cancer Prev Res; 8(11); 1027–35. ©2015 AACR.

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Keywords

Cancer Prevention Personalized cancer prevention Carcinogenesis Premalignancy Epigenetics Head, Neck & Oral Cancers

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