Acral lentiginous melanoma (ALM) is the most common subtype of acral melanoma. Even though recent genetic studies are reported in acral melanomas, the genetic differences between in-situ and invasive ALM remain unclear. We aimed to analyze specific genetic changes in ALM and compare genetic differences between in-situ and invasive lesions to identify genetic changes associated with the pathogenesis and progression of ALM. We performed whole genome sequencing of 71 tissue samples from 29 patients with ALM. Comparative analyses were performed, pairing in-situ ALMs with normal tissues and, furthermore, invasive ALMs with normal and in-situ tissues. Among 21 patients with in-situ ALMs, 3 patients (14.3%) had SMIM14, SLC9B1, FRG1, FAM205A, ESRRA, and ESPN mutations, and copy number (CN) gains were identified in only 2 patients (9.5%). Comparing 13 invasive ALMs with in-situ tissues, CN gains were identified in GAB2 in 8 patients (61.5%), PAK1 in 6 patients (46.2%), and UCP2 and CCND1 in 5 patients (38.5%). Structural variants were frequent in in-situ and invasive ALM lesions. Both in-situ and invasive ALMs had very low frequencies of common driver mutations. Structural variants were common in both in-situ and invasive ALMs. Invasive ALMs had markedly increased CN gains, such as GAB2, PAK1, UCP2, and CCND1, compared with in-situ lesions. These results suggest that they are associated with melanoma invasion.

中文翻译：

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原位和侵袭性肢端雀斑黑色素瘤的比较全基因组测序分析：GAB2、PAK1、UCP2 和 CCND1 拷贝数增益显着增加与黑色素瘤侵袭相关。


肢端雀斑样黑色素瘤（ALM）是肢端黑色素瘤最常见的亚型。尽管最近报道了肢端黑色素瘤的遗传学研究，但原位 ALM 和侵入性 ALM 之间的遗传差异仍不清楚。我们的目的是分析 ALM 的特定遗传变化，并比较原位病变和侵袭性病变之间的遗传差异，以确定与 ALM 发病机制和进展相关的遗传变化。我们对 29 名 ALM 患者的 71 份组织样本进行了全基因组测序。进行比较分析，将原位 ALM 与正常组织配对，此外，将侵入性 ALM 与正常组织和原位组织配对。在 21 名原位 ALM 患者中，3 名患者 (14.3%) 存在 SMIM14、SLC9B1、FRG1、FAM205A、ESRRA 和 ESPN 突变，仅 2 名患者 (9.5%) 发现拷贝数 (CN) 增加。将 13 例侵袭性 ALM 与原位组织进行比较，在 8 名患者 (61.5%) 的 GAB2 中发现 CN 增益，在 6 名患者 (46.2%) 中发现 PAK1，在 5 名患者 (38.5%) 中发现 UCP2 和 CCND1。原位和侵袭性 ALM 病变中结构变异很常见。原位和侵入性 ALM 的常见驱动突变频率都非常低。结构变异在原位和侵入性 ALM 中都很常见。与原位病变相比，侵入性 ALM 显着增加了 CN 增益，例如 GAB2、PAK1、UCP2 和 CCND1。这些结果表明它们与黑色素瘤侵袭有关。