Abstract 4252: Redefining the DNA methylome of prostate cancer using DNA methylation arrays.

Abstract Prostate cancer (PCa) is the most common noncutaneous malignancy and a leading cause of cancer death among men. Clinically localized disease might be successfully treated whereas disseminated disease remains mostly lethal. During prostate cancer development and progression, tumor cells undergo abnormal epigenetic modifications, including DNA methylation alterations. DNA methylation is the most studied epigenetic alteration in human cancer, and is associated with transcriptional repression of both coding and non-coding regions of the genome. Aberrant DNA methylation is gaining force in the fields of cancer risk assessment, diagnosis and therapy monitoring in different cancer types, including prostate cancer. Importantly, aberrant hypermethylation is widespread during neoplastic alteration of prostate cells, suggesting that restoration of a normal prostate epigenome through treatment with demethylating drugs could be clinically beneficial. The main aim of this work was to identify new epigenetically downregulated CpG's in PCa, using the 450K cytosine microarray-based approach, followed by validation in a larger set of clinical samples. We used the Infinium HumanMethylation450 BeadChip (Illumina) to consistently and significantly detect CpG methylation changes in prostate cancer tissues in comparison with morphological normal prostate tissue. The selected genomic regions were validated by pyrosequencing. The methylation data were subsequently confirmed at mRNA level using qRT-PCR. To prove the functional role of aberrant DNA methylation, we also performed a treatment with 5-Aza-2′-Deoxycytidine in PCa cell lines. Our work might provide new translational applications to the clinical management of PCa patients, based on of DNA methylation changes in PCa. Citation Format: Joao Ramalho-Carvalho, Rui Henrique, Sergi Sayols, Antonio Gomez, Carmen Jerónimo, Manel Esteller. Redefining the DNA methylome of prostate cancer using DNA methylation arrays. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4252. doi:10.1158/1538-7445.AM2013-4252