In recent years there is a global effort to characterize the molecular changes associated with the pathogenesis of melanoma. Thus, it was possible to create specific drugs against these changes, which significantly increased the survival of patients with melanoma patients. The TCGA (The Cancer Genome Atlas), the major methylation analysis in this tumor type, included 80% of metastatic samples, which limits the understanding of epigenetic alterations involved in the melanoma initiation and progression, although this and other studies show the importance of this event in tumorigenesis of melanoma, decreasing the survival of patients and can be used as a biomarker of response to treatment. The Melanoma Research Group of Barretos Cancer Hospital, is performing the whole genomic sequencing of 100 samples (43% primary tumors and 57% metastatic) in the context of the International Cancer Genome Consortium (ICGC) aims to perform methylome of these samples to associated epigenetic to genetic events to contribute for the understanding of the natural history of melanoma. For this, we will validate 5 target metiloma genes in 300 patients (100 primary, 100 lymph node metastases and 100 distant metastases) and 40 nevi. We will confirm the epigenetic regulation of the 5 genes by immunohistochemistry in Tissue Microarray (TMA). Then, we will perform the modulation of the gene by CRISPR-Cas9 (silencing) or with plasmid (overexpression) in two established and one primary melanoma cell line. Finally, we will investigate whether this modulation has impact on tumorigenic capacity, proliferation, migration and invasion of these cell lines.
News published in Agência FAPESP Newsletter about the scholarship: