Identification of anaplastic lymphoma kinase break points and oncogenic mutation profiles in acral/mucosal melanomas

Authors

  • Hai-Tao Niu,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
    2. Melanoma Unit & Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China
    Current affiliation:
    1. Cancer Institute & Hospital, Chinese Academy of Medical Sciences (CAMS), Chaoyang District, Beijing City, China
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  • Qi-Ming Zhou,

    1. Department of Oncology, The Sixth People Hospital of Shenzhen, Shenzhen, China
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  • Fang Wang,

    1. Department of Molecular Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Qiong Shao,

    1. Department of Molecular Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Yuan-Xiang Guan,

    1. Department of Surgery of Stomach and Pancreas, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Xi-Zhi Wen,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
    2. Melanoma Unit & Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Li-Zhen Chen,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
    2. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Qi-Sheng Feng,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
    2. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
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  • Wei Li,

    1. Institute of Hepatology, The Third People's Hospital of Shenzhen, Shenzhen, China
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  • Yi-Xin Zeng,

    Corresponding author
    1. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
    • State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Xiao-Shi Zhang

    Corresponding author
    1. Melanoma Unit & Biotherapy Center, Sun Yat-sen University Cancer Center, Guangzhou, China
    • State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Hai-tao Niu and Qi-Ming Zhou contributed equally to this work.

CORRESPONDENCE Xiao-Shi Zhang and Yi-Xin Zeng, e-mails: zhangxsh@sysucc.org.cn; zengyx@sysucc.org.cn

Summary

Acral and mucosal melanomas, the two most common subtypes of melanoma in China, exhibit different genetic alterations and biologic behavior compared with other subtypes of melanomas. The purpose of this study was to identify the genetic alterations in patients with acral or mucosal melanomas in southern China. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) analysis, polymerase chain reaction (PCR), and quantitative real-time reverse transcriptase PCR (qRT-PCR) were used to assess the anaplastic lymphoma kinase (ALK) break points. Furthermore, a mass spectrometry–based genotyping platform was used to analyze 30 acral melanomas and 28 mucosal melanomas to profile 238 known somatic mutations in 19 oncogenes. ALK break points were identified in four acral cases (6.9%). Eight (13.8%) cases harbored BRAF mutations, six (10.3%) had NRAS mutations, four (6.9%) had KIT mutations, two (3.5%) had EGFR mutations, two (3.5%) had KRAS mutations, two (3.5%) had MET mutations, one (1.7%) had an HRAS mutation, and one (1.7%) had a PIK3CA mutation. Two cases exhibited co-occurring mutations, and one case with a BRAF mutation had a translocation in ALK. This study represents a comprehensive and concurrent analysis of the major recurrent oncogenic mutations involved in melanoma cases from southern China. These data have implications for both clinical trial designs and therapeutic strategies.

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