Schwendinger Simon, Jaschke Wolfram, Walder Theresa, Hench Jürgen, Vogi Verena, Frank Stephan, Hoffmann Per, Herms Stefan, Zschocke Johannes, Nguyen Van Anh, Schmuth Matthias, Jukic Emina
Institute of Human Genetics, Medical University Innsbruck, 6020 Innsbruck, Austria.
Department of Dermatology, Venereology and Allergy, Medical University Innsbruck, 6020 Innsbruck, Austria.
Diagnostics (Basel). 2025 Feb 21;15(5):531. doi: 10.3390/diagnostics15050531.
: Genetics and epigenetics play an important role in the pathogenesis of cutaneous melanoma. The majority of cases harbor mutations in genes associated with the MAPK signaling pathway, i.e., , , or . The remaining neoplasms, often located on acral sites, are condensed as the triple-wildtype subtype and are characterized by other molecular drivers. This study aimed to elucidate genetic and epigenetic differences within cutaneous melanoma and to compare it with melanocytic nevi. : DNA was extracted from archived tissue samples of cutaneous melanoma ( = 19), melanocytic nevi ( = 11), and skin controls ( = 11) and subsequently analyzed by massive parallel (next generation) gene panel sequencing and genome-wide DNA methylation array analysis. The sample size was increased by including repository data from an external study. : There were major differences in the genomic landscape of MAPK-altered and triple-wildtype cutaneous melanoma, the latter presenting with a lower number of mutations, a different pattern of copy number variants, and a low frequency of promoter mutations. Dimensional reduction of DNA methylation array analysis clearly separated cutaneous melanoma from melanocytic nevi but revealed no major differences between classical cutaneous melanoma and the triple-wildtype cases. However, it identified a possible biological subgroup characterized by intermediately methylated CpGs. : Dimensional reduction of methylation array data is a useful tool for the analysis of melanocytic tumors to differentiate between malignant and benign lesions and may be able to identify biologically distinct subtypes of cutaneous melanoma.
遗传学和表观遗传学在皮肤黑色素瘤的发病机制中起着重要作用。大多数病例在与丝裂原活化蛋白激酶（MAPK）信号通路相关的基因中存在突变，即 、 、 或 。其余肿瘤通常位于肢端部位，被归为三野生型亚型，其特征为其他分子驱动因素。本研究旨在阐明皮肤黑色素瘤内部的遗传和表观遗传差异，并将其与黑素细胞痣进行比较。：从皮肤黑色素瘤（ = 19）、黑素细胞痣（ = 11）和皮肤对照（ = 11）的存档组织样本中提取DNA，随后通过大规模平行（下一代）基因panel测序和全基因组DNA甲基化阵列分析进行分析。通过纳入一项外部研究的储存库数据增加了样本量。：MAPK改变型和三野生型皮肤黑色素瘤的基因组格局存在重大差异，后者的突变数量较少、拷贝数变异模式不同，且 启动子突变频率较低。DNA甲基化阵列分析的降维明显将皮肤黑色素瘤与黑素细胞痣区分开来，但经典皮肤黑色素瘤与三野生型病例之间未发现重大差异。然而，它确定了一个可能以中等甲基化的CpG为特征的生物学亚组。：甲基化阵列数据的降维是分析黑素细胞肿瘤以区分恶性和良性病变的有用工具，并且可能能够识别皮肤黑色素瘤的生物学上不同的亚型。
