Department of Dermatology, Asan Medical Center, Seoul, Korea.
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Dermatol. 2021 Jul;48(7):999-1006. doi: 10.1111/1346-8138.15841. Epub 2021 Apr 23.
Many studies have analyzed the genes related to melanoma. However, only a limited number of studies have been conducted to identify the genes that are involved in the invasion and metastasis of acral melanoma (AM). Here, we attempted to investigate the genetic mutations associated with invasion and metastasis of AM. We analyzed five multi-regional samples of primary and metastatic AM and histologically normal tissue adjacent to the tumor (NAT) in two AM patients by whole-exome sequencing (WES). We identified single nucleotide variations and small indels present in tissue samples but not in saliva. We compared the sequencing results of superficial and deep lesions and primary and metastatic lesions of AM. We identified significantly deleterious mutations (SDM) that are likely to be related to invasion and metastasis of AM, respectively. SDM such as SKA3, MAST4, CNNM1, KIAA1549L, and SLC26A10 were found only in the deep lesion, but not in the superficial lesion. SDM present only in the metastatic lesion were ANO1, CPEB1, EP300, INADL, MAP1B, MAP7D1, MARCH6, NETO1, PRKCE, SBK1, TNRC6A, USP13, WDR74, and ZNF827. In conclusion, we applied multi-region WES to investigate possible pathogenic mutations related to invasion and metastasis in AM. Several genes including CNNM1, USP13, ZNF827, WDR74, CPEB1, and EP300 might be related to invasion and metastasis of AM. This study might facilitate the exploration of the evolutionary pathogenesis of advanced AM.
许多研究分析了与黑色素瘤相关的基因。然而，只有有限的研究旨在鉴定参与肢端黑色素瘤（AM）侵袭和转移的基因。在这里，我们试图研究与 AM 侵袭和转移相关的遗传突变。我们通过全外显子组测序（WES）分析了两名 AM 患者的五个原发和转移性 AM 及肿瘤旁组织（NAT）的多区域样本。我们鉴定了组织样本中存在但唾液中不存在的单核苷酸变异和小插入缺失。我们比较了 AM 的浅表和深部病变、原发和转移性病变的测序结果。我们分别鉴定了可能与 AM 侵袭和转移相关的显著有害突变（SDM）。仅在深部病变中发现 SKA3、MAST4、CNNM1、KIAA1549L 和 SLC26A10 等 SDM，而在浅表病变中未发现。仅在转移性病变中存在的 SDM 有 ANO1、CPEB1、EP300、INADL、MAP1B、MAP7D1、MARCH6、NETO1、PRKCE、SBK1、TNRC6A、USP13、WDR74 和 ZNF827。总之，我们应用多区域 WES 研究了 AM 侵袭和转移中可能的致病突变。包括 CNNM1、USP13、ZNF827、WDR74、CPEB1 和 EP300 在内的几个基因可能与 AM 的侵袭和转移有关。这项研究可能有助于探索晚期 AM 的进化发病机制。
