The pathogenesis of melanomas emerging in plantar surfaces remains unclear; however, mechanical stress has been reported to increase the formation of melanomas.,In this study, we conducted a multicenter retrospective analysis of 153 acral melanomas diagnosed between 2000 and 2015 in Taiwan.,The male-to-female ratio of the patients in question was 1:1.28, and the mean age at diagnosis was 68 years.,We examined whether melanomas which developed in different areas of the patients’ soles differed in their associations with various clinicopathological characteristics and survival.,Testing by goodness of fit indicated that stress-bearing areas were significantly more conducive to the generation of melanomas than non-stress-bearing areas (P < 0.0001).,More specifically, compared to the arch, the rear of the foot and front of the foot were significantly more conducive to the generation of melanomas (P < 0.0001 and P < 0.0001, respectively).,The distribution pattern was not associated with differences in age, gender, right/left foot involvement, ulceration, mitosis, lymph node metastasis, tumor thickness, or stage.,The overall, distant metastasis-free, and recurrence-free survival rates did not differ significantly between the stress-bearing and non-stress-bearing areas.,Furthermore, while acral melanomas tended to develop on stress-bearing areas, the distribution pattern was not associated with the prognostic index or survival.
Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of non-ultraviolet (UV)-derived CMs remains limited.,Deeper analysis of acral lentiginous melanoma (ALM), a rare sun-shielded melanoma subtype associated with worse survival than CM, is needed to delineate non-UV oncogenic mechanisms.,We thus performed comprehensive genomic and transcriptomic analysis of 34 ALM patients.,Unlike CM, somatic alterations were dominated by structural variation and absence of UV-derived mutation signatures.,Only 38% of patients demonstrated driver BRAF/NRAS/NF1 mutations.,In contrast with CM, we observed PAK1 copy gains in 15% of patients, and somatic TERT translocations, copy gains, and missense and promoter mutations, or germline events, in 41% of patients.,We further show that in vitro TERT inhibition has cytotoxic effects on primary ALM cells.,These findings provide insight into the role of TERT in ALM tumorigenesis and reveal preliminary evidence that TERT inhibition represents a potential therapeutic strategy in ALM.