IDENTIFICATION IN SILICO DE STRATIFINA (SFN) WITH A NEW GENE PUTATIVE HIDROXIMETILATION IN BREAST CANCER

Darley de Lima Ferreira Filho, Nara Barbosa Araújo, Roberta Luciana do Nascimento Godone, Carlos Henrique Madeiros Castelletti, Glauber Moreira Leitão, Nancy Cristina Ferraz de Lucena Ferreira, Danyelly Bruneska Gondim Martins, José Luiz de Lima Filho

Laboratório de Imunopatologia Keizo Asami/LIKA – UFPE.INTRODUCTIONThe 5-HMC is a 5-MC conversion product by the TET hydroxylase family. 5-HMC was proposed to be a stable intermediate between methylation and demethylation steps and raised questions about its function in the regulation of genes. Evidence suggests that while 5-MC in the promoter region represses transcription; 5-HMC, especially on the bodies of genes, is associated with increased gene expression. Overall loss of 5-HMC has been described in breast cancer. However, few studies have determined the genes in which 5-HMC is low, especially in breast cancerOBJECTIVE:Identify by in silico analysis new putative genes that are hydroxymethylated in gene bodies and also described as hypermethylated in the promoter in breast tumors, since these two epigenetic mechanisms of gene regulation are well related.RESULTS:In 159 cases of breast cancer evaluated in the period from January 2015 to October 2015 at Barão de Lucena Hospital, in only 25 cases the LZTS1 gene was identified and it met our criteria. LZTS1, a classic tumor suppressor gene, has been described with lower levels of 5-HMC and also hypermethylated in breast cancer compared to normal breast cancer. In order to find novel putative hydroxymethylated genes related to breast cancer, we crossed a list of 51 genes hypermethylated on the promoter region in breast tumors obtained through MetaCoreTM with a list of genes described by showing specific hydroxymethylation peaks In gene bodies, from a genomic mapping of 5-HMC in humans. When these two lists were overlapped, only the Stratifin gene (SFN) remained. The SFN gene is a p53-regulated inhibitor of G2 / M progression, and is involved in apoptosis. CONCLUSION: We identified SFN as a gene under 5-HMC influences, which is also hypermethylated in breast tumors. Since epigenetic changes are reversible, the identification of 5-HMC rule in specific genes may be useful as a molecular target pathway for more effective therapy.

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