Treatment and Diagnostic for Melanomas

Children's Hospital Boston
posted on 07/01/2010

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Melanoma is an aggressive malignancy which often first presents with advanced metastasis and for which treatment options are limited. In an effort to identify novel targets for the treatment of melanoma, Dr. Zon's lab has designed and performed a screen using a zebrafish model system of melanoma induced by the oncogenic BRAF-V600E mutation and deficiency for the p53 tumor suppressor, mutations which are commonly seen in human melanomas. Screening for genes capable of enhancing the generation of melanoma, the lab identified the SETDB1 gene, encoding a histone-lysine N-methyltransferase responsible for trimethylation of lysine 9 on histone H3, a specific tag for epigenetic transcriptional repression. || Since the human SETDB1 gene is within a chromosomal region known to be amplified in human melanoma, this finding may provides a marker for melanoma diagnostics and a prognostic marker useful for identifying a subset of melanomas which have a more aggressive clinical course. Further, the studies indicate that overexpression of SETDB1 leads to more aggressive melanomas with enhanced local invasiveness. This suggests that SETDB1 may be an attractive target for therapeutics in treating human melanoma and other malignancies with BRAF-V600E mutations or other Ras pathway overactivation.