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- W2253491555 abstract "20028 Characterization of the different molecular mechanisms involved in development and progression of melanoma (referred to as melanomagenesis) could represent a potential tool to identify the molecular profiles underlying aggressiveness, clinical behavior, or response to therapy as well as to better classify the subsets of melanoma patients with different prognosis.Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in molecular pathways within the melanocytic lineage. Putting together all recent molecular findings from our group and from literature, we assessed a model of pathogenesis of melanoma, in which we could allocate the different alterations into three sequential phases of melanocytic transformation: 9p21 allelic deletions, BRAF activation, and AKT overexpression (for melanocytic proliferation); impairment of p16-RB and p14-p53 pathways, CyclinD1 overexpression, and PTEN inactivation (for melanoma development); NRAS activation, loss of p16CDKN2A, silencing of PTEN, activation of NF-kB, and MITF gene amplification (for melanoma progression). Different molecular pathways associated with the melanomagenesis may correspond to different subsets of melanoma patients, whose identification should be introduced in clinical trials. Indeed, tissue sections from each melanoma patient should be evaluated through: immunohistochemistry, using antibodies against the main candidate proteins (p16CDKN2A, p14CDKN2A, phosphoERK1/2, phosphoRB, p10, p53, CyclinD1), in order to assess any variation of their expression levels, and fluorescence in situ hybridization (FISH) analysis, in order to evaluate the existence of pathogenetic gene amplifications (for MITF, CyclinD1 or CDK4 genes). These findings along with the advancements of the biotechnologies will do provide even more reliable tools for detailed molecular analyses, allowing to better characterize new biomarkers which may predict prognosis and response to treatment in patients with melanoma. No significant financial relationships to disclose." @default.
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- W2253491555 date "2008-05-20" @default.
- W2253491555 modified "2023-10-18" @default.
- W2253491555 title "Molecular classification for the management of melanoma patients" @default.
- W2253491555 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.20028" @default.
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