A potential predictive marker for response to interferon in malignant melanoma

Abstract

The methylthioadenosine phosphorylase (mtap) gene is localized on chromosome 9p21, a chromosomal region often affected by deletion in several kinds of malignant tumors. Studies on malignant melanoma have revealed loss of MTAP expression in vitro and in vivo; however, loss of MTAP expression is mainly regulated by promoter hypermethylation. Loss of MTAP was shown to have an effect on tumor invasion and metastasis. In a recent study, MTAP not only had a role as tumor suppressor but was also implicated in lack of therapeutic response of patients with recurrent malignant melanoma. There is evidence that loss of MTAP results in an inhibition of STAT signaling pathways regulated by interferon. This in turn leads to ineffectiveness of interferon therapy. Determination of the MTAP status in the primary tumor could, therefore, potentially lead to a selection of patients who benefit from interferon treatment.