journal contribution
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 <p>Supplementary Table 1: Description of the studies used for the in silico validation of the candidate genes in terms of number of samples analyzed, platform used and number of overlapping genes between our candidate gene list and the genes analyzed on the platform (HN: head and neck; SCC: squamous cell carcinoma). Supplementary Table 2: List of cell lines in which the level of promoter methylation of AGTR1, FOXI2, HOXA9, PENK and ZIC1 were evaluated (HNSCC: head and neck squamous cell carcinoma). Supplementary Table 3: Univariate Cox proportional hazards model for all other available variables. Supplementary table 4: Multi-covariable Cox Model analysis including histology (hyperplasia or dysplasia).</p>
History
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.
