TSLC1 gene silencing in cutaneous melanoma

Abstract

Tumor suppressor in lung cancer 1 (TSLC1) is a tumor suppressor gene that encodes a member of the immunoglobulin superfamily, which is involved in the progression of some types of cancer. Several studies have shown that loss of TSLC1 expression is strongly correlated to methylation of the gene promoter, thus leading to poor prognosis in these cancers. However, the role of TSLC1 in cutaneous melanoma (CM) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of TSLC1 inactivation in CM. The expression and promoter methylation of TSLC1 were analyzed in 120 CMs. TSLC1 expression was examined by immunohistochemistry, whereas its methylation status was determined by methylation-specific PCR. TSLC1 expression was lost in 84 of 120 (70%) CMs; 36 (30%) CMs were scored as positive for TSLC1 protein expression. The TSLC1 promoter was methylated in 58 (48.33%) of 120 CMs. The incidence of the loss of expression and methylation of TSLC1 significantly increased as the tumor stage advanced (P=0.032 and 0.0021, respectively). Furthermore, in CM, disease-related survival was significantly shorter in patients with tumors losing TSLC1 or harboring methylated TSLC1 (P=0.0003 and 0.0329, respectively). The epigenetic silencing of TSLC1 through methylation is an important event in the pathogenesis of CM, and TSLC1 provides an indicator for poor prognosis.