Promoter Methylation of PTEN is a Significant Prognostic Factor in Melanoma Survival.
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Structural compromise of the tumor suppressor gene, PTEN occurs in 10% of melanoma specimens and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features and its impact on the outcome of melanoma patients. PTEN promoter methylation data was acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma cohort (TCGA-MEL). Hierarchical clustering was performed to identify PTEN "high methylated" and "low methylated" samples. Subsequently, differences in clinical features and outcomes based on PTEN promoter methylation status were then analyzed using SPSS and R. In the KMC, all tumors were acquired from primary tumors and 65.7% (n=105) were acral or mucosal by site, whereas in TCGA-MEL, 90.5% of the tumors were from regional lymph node and distant metastatic lesions. Overall, 17.7% and 45.7% of the specimens harbored BRAF mutations in the KMC and TCGA-MEL, respectively. NRAS was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL, respectively. In KMC, 31 cases (19.6%) were included in the high methylated group versus 142 cases (60.7%) in the TCGA-MEL cohort (P<0.001). Multivariate Cox-regression analysis revealed promoter methylation of PTEN to be an independent negative prognostic factor for survival in both the KMC (HR 3.76, 95% CI=1.24 to 11.12, P=0.017) and TCGA-MEL (HR 1.88, 95% CI=1.13 to 3.12, P=0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in melanoma patients.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Journal of Investigative Dermatology|
|Early online date||2016 Feb 5|
|Publication status||Published - 2016|