Abstract 4809: Epigenomic profiling of oral cancer

Abstract

Abstract Despite combined surgery and radiation therapy, long-term survival for oral cancer has not improved over the past several decades. This is primary due to poor clinical prognosis of patients with the lymph nodes metastasis. Therefore, deeper understanding of the molecular basis of highly malignant property and patient stratification along with these characters are needed. Although, recent genome-wide analyses of DNA methylation have revealed a large number of aberrantly methylated genes in many cancers, and allowed us to identify the molecularly defined subgroups such as CpG island methylation phenotype (CIMP) in certain tumors, the methylation diversity of clinical oral cancers are still unknown. The purpose of this study is to characterize DNA methylation profiles of oral cancer tissues (six normal oral mucosal swab, three non-cancerous mucosal tissues, and fifty-nine oral cancer tisseus) and to identify the specific methylation pattern related to the clinical features. Genome-wide methylation analysis was performed using Infinium HumanMethylation27 BeadArray system, which can analyze methylation status of 27,000 CpG sites semi-quantitatively, using 500ng of genomic DNA.We found 2,762 aberrantly methylated CpG sites in oral cancers against normal mucosa. By unsupervised clustering analysis, oral cancer could be divided into two methylation epigenotypes that are significantyly correlated with high incidence of lymph node metastasis and poor differentiation. We obtained the highly predictive candidates of classifier genes and they were confirmed by MassARRAY analysis. In summary, we identified two methylation epigenotypes related with clinical outcome in oral cancer, and candidate classifier genes would be useful clues of patient stratification for intensive therapy to overcome the tumor recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4809. doi:10.1158/1538-7445.AM2011-4809