Abstract 4090: Epigenetic profiling identifies differentially methylated loci in metastatic vs. non-metastatic primary squamous and basal cell skin cancers

Abstract

Abstract Nonmelanoma skin cancer is the most commonly diagnosed cancer in the United States. Over 2 million new cases of these cancers are diagnosed each year, and incidence rates are increasing worldwide. Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin are generally considered less aggressive than melanomas, which is reflected in their lower relative mortality rates. Despite this, a clinically relevant subgroup of both of these cancers will metastasize and develop an aggressive disease phenotype. In order to characterize the molecular pathways that may be involved in the development of metastatic disease in these common cancers, we measured DNA methylation profiles at 1505 CpG sites associated with 807 related to cancer using the Illumina Goldengate Methylation Cancer Panel BeadArray in BCCs and SCCs isolated from patients treated at the University of Michigan. DNA methylation was measured in metastatic (n=9) and non-metastatic (n=19) primary SCCs and in metastatic (n=3) and non-metastatic (n=9) primary BCCs. Due to the known divergent mechanisms of carcinogenesis of basal and squamous cell carcinomas, separate analyses were conducted for these tumor types. Unsupervised hierarchical clustering was used to identify overall differences in DNA methylation patterns between metastatic and non-metastatic disease. Gene specific analyses using linear modeling coupled with an empirical Bayes method of variance estimation were conducted to identify if methylation at individual CpG sites is associated with metastatic potential. SCCs were not found to cluster based on metastasis, however, metastatic BCCs were found to cluster together, suggesting that metastatic BCCs may share common mechanisms of pathogenesis. In gene specific analyses, FRZB was found to be statistically significantly hypermethylated in metastatic compared to non-metastatic primary SCCs (median methylation: 54.2% vs. 4.7%; p=3.8x10-5). Two sites in MYCL2 were found to be significantly hypomethylated in metastatic vs. non-metastatic BCCs (3.7% and 4.0% vs. 77.9% and 53.5%; p=1.87x10-6 and 3.69x10-5 respectively). The results from this pilot study give insight into the molecular mechanism of metastasis for nonmelanoma skin cancers and identify the divergent characteristics of BCCs and SCCs. The differentially methylation regions identified in this study may be useful epigenetic biomarkers of metastatic potential for nonmelanoma skin cancers to be examined in an extended patient population in future studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4090. doi:1538-7445.AM2012-4090