Human melanoma presents extreme chemoresistance and poor prognosis with a higher risk of lymphatic and hematogenous metastases, besides six to nine months of survival rate. There is no drug efficient in spite of recent advances in therapy as the verumafenib and ipilimumab, since the patients have still shown chemoresistance and tumor recurrence. The current treatment, therefore, is still based on the same used in the past decades even despite the improved therapeutic technology. Therefore, to know the biology of melanoma and to seek new targets are proeminent aims in this area. Tumor progression can be controlled by epigenetic events such as hypermethylation of tumor suppressor genes that are silenced during malignant transformation. The modulation of methylation is a promising therapeutic target because it can be reversed by treatment with demethylant agents, characterizing the epigenetic therapy. RECK gene is expressed in various normal human tissues, but it is suppressed during neoplastic transformation, and its silencing may be due to hypermethylation of its promoter. ALX3 gene presents its promoter hypermethylation in tumors of advanced stage neuroblastoma and colorectal tumors, however so far not been established the participation of these genes in transformation and evolution of melanoma. However, recently described that there are two transcripts from the chimeric fusion (exon 13/RECK gene and exon 3/ALX3 gene, and exon 14/RECK gene and exon 4/ALX3 gene). Although these transcripts do not generate functional chimeric protein, such a phenomenon, although rare, could illustrate a possible mechanism of suppression of RECK in melanoma and also elucidate the role of ALX3 in the progression of this tumor, which is the hypothesis of this work. Techniques of cellular and molecular biology, such as gene silencing and overexpression, Western blot,and quantitative PCR will be used to evaluate the expression and the methylation levels of RECK/ALX3, seeking to elucidate the role of such genes in melanoma.
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