Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-11-20 DOI:10.1002/cam4.70360

Tokimasa Hida, Masashi Idogawa, Junji Kato, Yukiko Kiniwa, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Shoichiro Tange, Masae Okura, Ryuhei Okuyama, Takashi Tokino, Hisashi Uhara

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Abstract

Background

Acral and mucosal melanomas are more prevalent in Asians than in Caucasians, unlike cutaneous melanomas, which are predominant in Caucasians. Recent studies have suggested that non-Caucasian cutaneous melanomas responded less to immune checkpoint inhibitors, highlighting the need for genetic profiling across ethnicities. This study aimed to elucidate the genetic characteristics of Japanese melanomas, which is an under-researched topic.

Methods

Single-nucleotide variants, indels, and copy number alterations in 104 Japanese melanoma patients (37 cutaneous, 52 acral, and 15 mucosal) were analyzed using custom panel sequencing.

Results

Driver events were detected in 94% of the cases. Among cutaneous melanoma cases, 76% had BRAF mutations, and 8% had NRAS mutations. In acral melanoma, BRAF (9%), NRAS (17%), KRAS (8%), KIT (19%), and NF1 (7%) mutations were detected. Major driver mutations in mucosal melanoma were detected in NRAS, KRAS, NF1, PTEN, GNAQ, and KIT. The median tumor mutational burden across all melanoma types was 4.6 mutations/Mb, with no significant difference between the cutaneous and acral/mucosal types. Of the 21 patients with both primary and metastatic lesions, 11 showed distinct mutations in each. Potentially actionable mutations were detected in 58 patients in addition to BRAF V600E/K mutations in 31.

Conclusions

This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

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日本皮肤、口腔和粘膜黑色素瘤的遗传特征

背景口腔和粘膜黑色素瘤在亚洲人中的发病率高于白种人，这与皮肤黑色素瘤主要发生在白种人中不同。最近的研究表明，非白种人皮肤黑色素瘤对免疫检查点抑制剂的反应较小，这凸显了跨种族基因分析的必要性。本研究旨在阐明日本人黑色素瘤的遗传特征，这是一个研究不足的课题。方法采用定制面板测序法分析了 104 例日本黑色素瘤患者（37 例皮肤癌、52 例尖锐湿疣和 15 例粘膜癌）的单核苷酸变异、嵌合体和拷贝数改变。结果 94% 的病例检测到了驱动基因事件。在皮肤黑色素瘤病例中，76%有BRAF突变，8%有NRAS突变。在口腔黑色素瘤中，发现了BRAF（9%）、NRAS（17%）、KRAS（8%）、KIT（19%）和NF1（7%）突变。粘膜黑色素瘤的主要驱动基因突变在NRAS、KRAS、NF1、PTEN、GNAQ和KIT中均有检测到。所有黑色素瘤类型的肿瘤突变负荷中位数为4.6个突变/Mb，皮肤型和口腔/粘膜型之间没有明显差异。在21名同时患有原发性和转移性病灶的患者中，有11名患者的两种病灶都出现了不同的突变。除了 31 例患者的 BRAF V600E/K 基因突变外，58 例患者还检测到了可能具有可操作性的基因突变。结论本研究强调了日本黑色素瘤患者的不同基因异常和可作用变异。这表明东亚皮肤黑色素瘤的肿瘤突变负荷较低，可能会影响免疫检查点抑制剂的疗效。个体间和个体内驱动基因突变的异质性凸显了个性化治疗方法的必要性。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.