PTEN Promoter Hypermethylation Is Associated with Breslow Thickness in Acral Melanoma on the Heel, Forefoot, and Hallux

Abstract

BackgroundAcral melanoma occurs on glabrous skin or the nail apparatus and is distinct from ultraviolet-related melanoma due to differing genetic alteration patterns. Although the pathogenesis of acral melanoma is not well understood, mechanical stress is thought to induce acral melanoma. The incidence of gene mutation and promoter methylation has been reported in tumors from acral melanoma; however, an association between genetic/epigenetic alterations and mechanical stress in acral melanoma remains unclear.ObjectiveTo investigate the relationship between clinical/genetic factors and mechanical stress in acral melanoma.MethodsA retrospective review of 52 patients diagnosed with acral melanoma was performed. We reviewed the clinical characteristics of patients, tumor status, and tumor location. Mutations in BRAF, NRAS, and the TERT promoter, along with KIT amplification and PTEN promoter methylation were analyzed in the tumors.ResultsThe heel (34/52, 65.4%) was the most common anatomical tumor site. Mutations in BRAF (6/48, 12.5%), NRAS (6/49, 12.2%), and the TERT promoter (4/33, 12.1%), along with KIT amplification (3/37, 8.1%) and PTEN promoter hypermethylation (12/48, 25.0%) were observed in the tumors. On the forefoot, heel, and hallux, PTEN promoter hypermethylation was significantly associated with Breslow thickness (p=0.001) and ulceration rate (p=0.042). On the midfoot and lesser toes, there was no significant difference in Breslow thickness or ulceration rate regardless of PTEN promoter hypermethylation (p>0.05).ConclusionPTEN promoter hypermethylation is associated with Breslow thickness and tumor ulceration on the forefoot, heel, and hallux in acral melanoma in Korean patients.