Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma

Abstract

Aberrant methylation of TSGs is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.

Aberrant DNA Methylation Predicts Melanoma-Specific Survival in Patients with Acral Melanoma

“…In agreement with previous studies on CM, we identified significant associations between aberrant methylation and aggressive clinicopathologic parameters in AM including the presence of lymph node metastasis, ulceration, increased mitoses, and higher Breslow thickness [21][22][23][24][25][26]. In addition, our study revealed significant correlation between aberrant methylation of HHEX, DIPK2A, NELFB/COBRA1, CDH13, TEF, IFITM1, and SIK3 and worse DSS.…”

“…Recent studies have revealed that promoter methylation of PTEN is an independent predictor of worse survival in melanoma [19,20]. Methylation of RARB, APC, CDH13, ESR1, CDKN2A, RASSF1, MGMT, and HOXD9 has been shown to be associated with poor survival in CM [21][22][23][24][25][26]. AMs have relatively greater prevalence of DNA methylation than other types of CM and are significantly associated with PTEN and CDH13 hypermethylation [21].…”

“…Methylation of RARB, APC, CDH13, ESR1, CDKN2A, RASSF1, MGMT, and HOXD9 has been shown to be associated with poor survival in CM [21][22][23][24][25][26]. AMs have relatively greater prevalence of DNA methylation than other types of CM and are significantly associated with PTEN and CDH13 hypermethylation [21]. Genome-wide mapping of 5-hydroxymethylcytosine revealed its loss in melanoma, and restoring active TET2 or IDH2 reactivated 5-hydroxymethylcytosine suppressed melanoma growth and increased tumor-free survival in animal models, suggesting the therapeutic potential of targeting epigenetic changes [27,28].…”

“…Despite promising clinical responses to immune checkpoint blockade therapy and targeted therapy, the response of ALM to these agents remains unpredictable, underscoring a critical need to delineate additional prognostic and predictive biomarkers and/or novel therapeutic targets for this disease. To date, few studies have focused on identifying epigenetic prognostic biomarkers in AM [21]. Here, we subclassified AMs into primary ALM (PALM), non-ALM-type melanomas involving acral skin (NALM, defined as AM that lacks lentiginous pattern of intraepidermal melanocytic growth; includes superficial spreading, lentigo maligna, and nodular types), and metastatic ALM (MALM), and interrogated the methylation profiles of AMs and primary non-acral CM (PCM).…”

MicroRNA-21-Enriched Exosomes as Epigenetic Regulators in Melanomagenesis and Melanoma Progression: The Impact of Western Lifestyle Factors

“…To clarify the pathogenesis of MM, efforts have been focused on the identification of MM oncogenes, such as NRAS, BRAF, PTEN, MITF, NEDD9, hTERT and KIT , which have led to an improved understanding of MM etiology and opened new avenues for personalized treatment [ 5 , 6 , 7 , 8 , 9 , 10 ]. However, not only genetic deviations promote MM initiation, proliferation and progression but also epigenetic mechanisms including aberrant DNA- methylations and changes in microRNA (miR) expression, extensively reviewed elsewhere [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. The present review focuses on miR-21, which is a key oncogenic miR overexpressed in MM, glioblastoma and other common cancers of Western societies [ 24 , 25 , 26 , 27 ].…”