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Promoter Methylation of PTEN Is a Significant Prognostic Factor in Melanoma Survival.

 Mi Ryung Roh  ;  Sameer Gupta  ;  Kyu-Hyun Park  ;  Kee Yang Chung  ;  Martin Lauss  ;  Keith T. Flaherty  ;  Go¨ran Jo¨nsson  ;  Sun Young Rha  ;  Hensin Tsao 
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.136(5) : 1002-1011, 2016 
Journal Title
Issue Date
Adult ; Aged ; Chi-Square Distribution ; Cluster Analysis ; Cohort Studies ; DNA Methylation* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Melanoma/genetics* ; Melanoma/mortality* ; Melanoma/therapy ; Middle Aged ; Multivariate Analysis ; PTEN Phosphohydrolase/genetics* ; Prognosis ; Promoter Regions, Genetic/genetics ; Proportional Hazards Models ; Risk Assessment ; Skin Neoplasms/genetics* ; Skin Neoplasms/mortality* ; Skin Neoplasms/therapy ; Statistics, Nonparametric ; Survival Analysis
Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (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 patients with melanoma. PTEN promoter methylation data were acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma (TCGA-MEL) cohort. 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 the TCGA-MEL cohort, 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 cohort, respectively. Neuroblastoma RAS viral oncogene homolog was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL cohort, respectively. In the 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 (hazard ratio 3.76, 95% confidence interval = 1.24-11.12, P = 0.017) and TCGA-MEL cohort (HR 1.88, 95% confidence interval = 1.13-3.12, P = 0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in patients with melanoma.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Roh, Mi Ryung(노미령) ORCID logo https://orcid.org/0000-0002-6285-2490
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chung, Kee Yang(정기양) ORCID logo https://orcid.org/0000-0003-3257-0297
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