Supplementary Material for: Molecular Profile of Subungual Melanoma: a MelaNostrum Consortium Study of 68 Cases Reporting BRAF, NRAS, KIT, and TERT promoter status.

Background: Subungual melanoma (SM) is an unusual type of melanocytic tumor affecting the nail apparatus. The mutational prevalence of the most prominently mutated genes in melanoma has been reported in small cohorts of SM, with unclear conclusions on whether SM is different from the rest of melanomas arising in acral locations or not. Hence, the molecular profile of a large series of SM is yet to be described. Objectives: The aim of this study was to describe the molecular characteristics of a large series of SM and their association with demographic and histopathological features. Methods: Patients diagnosed with SM between 2001 and 2021 were identified from six Spanish and Italian healthcare centers. The mutational status for BRAF, NRAS, KIT, and the promoter region of TERT (TERTp) were determined either by Sanger sequencing or Next-Generation Sequencing. Clinical data were retrieved from the hospital databases to elucidate potential associations. Results: A total of 68 SM cases were included. Mutations were most common in BRAF (10.3%) and KIT (10%), followed by NRAS (7.6%), and TERTp (3.8%). Their prevalence was similar to that of non-subungual acral melanoma, but higher in SM located on the hand than on the foot. Conclusions: To date, this study represents the largest cohort of SM patients with data on the known driver gene mutations. The low mutation rate supports a different etiopathogenic mechanism for SM in comparison of non-acral cutaneous melanoma, particularly for SM of the foot.

背景：甲下黑色素瘤（subungual melanoma, SM）是一类累及甲单位的罕见黑素细胞肿瘤。既往针对小型甲下黑色素瘤队列的研究仅报道了黑色素瘤中最常见突变基因的突变率，但尚未明确甲下黑色素瘤与其他肢端来源黑色素瘤是否存在差异。因此，大样本甲下黑色素瘤队列的分子特征仍有待阐明。
研究目的：本研究旨在阐明大样本甲下黑色素瘤队列的分子特征，及其与人口学特征、组织病理学特征的关联。
研究方法：本研究纳入2001年至2021年间于6家西班牙及意大利医疗中心确诊的甲下黑色素瘤患者。采用桑格测序（Sanger sequencing）或下一代测序（Next-Generation Sequencing, NGS）检测BRAF、NRAS、KIT基因及TERT启动子区域（TERTp）的突变状态。从医院数据库中提取临床数据，以分析潜在的关联关系。
研究结果：本研究共纳入68例甲下黑色素瘤病例。突变检出率最高的基因为BRAF（10.3%）与KIT（10%），其次为NRAS（7.6%）及TERTp（3.8%）。其突变率与非甲下型肢端黑色素瘤相近，但手部甲下黑色素瘤的突变率高于足部甲下黑色素瘤。
研究结论：截至目前，本研究是首个纳入已知驱动基因突变数据的最大规模甲下黑色素瘤患者队列。较低的突变率提示，甲下黑色素瘤（尤其是足部甲下黑色素瘤）的致病机制与非肢端皮肤黑色素瘤存在差异。