北京大学Lu Si等研究人员合作发现，基因组特征揭示东亚地区掌趾部黑色素瘤的独特突变景观。相关论文于2025年1月9日在线发表在《遗传学报》上。

研究人员旨在全面分析东亚人群掌趾部黑色素瘤的基因组特征。研究人员对55个掌趾部黑色素瘤肿瘤进行了全基因组测序，并结合相关临床数据进行数据挖掘。研究结果揭示了东亚掌趾部黑色素瘤的独特突变特征，表现为较少的点突变和结构变异，NRAS突变的发生率较高，而相较于欧洲裔患者，BRAF突变的发生率较低。

值得注意的是，研究人员识别出先前被低估的紫外线辐射特征，并发现其与BRAF和NRAS突变显著相关。结构重排特征表明，BRAF驱动的肿瘤与NRAS驱动的肿瘤存在不同的突变过程。

研究人员还发现，同源重组缺陷与MAPK通路突变相关联，且与较差的预后相关。EP300、TERT、RAC1和LZTR1中的结构变异和扩增提示了针对东亚人群的潜在新型治疗靶点。BRAF/NRAS突变肿瘤中全基因组重复事件的高发生率表明可能存在协同致癌效应，值得进一步研究。总之，该研究为东亚人群掌趾部黑色素瘤的遗传基础提供了重要见解，为靶向治疗创造了机会。

据了解，掌趾部黑色素瘤是东亚地区最常见的黑色素瘤亚型，通常与较差的预后相关。

附：英文原文

Title: Genomic characterization reveals distinct mutational landscape of acral melanoma in East Asian

Author: Jiayan Wu b c d, Yan Kong a, Lu Si a

Issue&Volume: 2025/01/09

Abstract: Acral melanoma, the most common melanoma subtype in East Asia, is associated with a poor prognosis. This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians. We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data. Our findings reveal a unique mutational profile in East Asian acral melanoma, characterized by fewer point mutations and structural variations, a higher prevalence of NRAS mutations, and a lower frequency of BRAF mutations compared to patients of European descent. Notably, we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations. Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors. We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis. The structural variations and amplifications in EP300, TERT, RAC1, and LZTR1 point to potential novel therapeutic targets tailored to East Asian populations. The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation. In summary, our study provides important insights into the genetic underpinnings of acral melanoma in East Asians, creating opportunities for targeted therapies.

DOI: 10.1016/j.jgg.2024.12.018

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724003710