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

Fenghao Zhang; Xiaowen Wu; Tao Jiao; Haizhen Du; Qian Guo; Chuanliang Cui; Zhihong Chi; Xinan Sheng; Dezhi Jiang; Yuhong Zhang; Jiayan Wu; Yan Kong; Lu Si

doi:10.1016/j.jgg.2024.12.018

Volume 52 Issue 4

Apr. 2025

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Article Navigation > Journal of Genetics and Genomics > 2025 > 52(4): 525-538

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

doi: 10.1016/j.jgg.2024.12.018

a. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Research Institute, Beijing 100142, China;
b. Beijing Kanghui Biotechnology Co. LTD, Beijing 100101, China;
c. Clinical Research Division of Berry Oncology Corporation, Beijing 102206, China;
d. Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, Fujian 350020, China

Funds:

This work was supported by the National Key Research and Development Program (2023YFC2506404), the Natural Science Foundation of China (82272848, 82425047, 82272676), Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20220901), Beijing Natural Science Foundation (7242021, L248021), Sichuan Provincial Science and Technology Department Key Research and Development Program (2024YFHZ0004).

Received Date: 2024-12-17
Accepted Date: 2024-12-24
Rev Recd Date: 2024-12-24

Available Online: 2025-07-11

Publish Date: 2025-01-09

Abstract

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 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.
- Acral melanoma,
- Whole-genome sequencing,
- Genomic characteristics,
- MAPK pathway,
- Structural variations,
- East Asian

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