title: Identification of anaplastic lymphoma kinase break points and oncogenic mutation profiles in acral/mucosal melanomas.
abstract: 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Niu
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shao
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Guan
authors.forename: Xi-Zhi
authors.initials: XZ
authors.lastname: Wen
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Chen
authors.forename: Qi-Sheng
authors.initials: QS
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Xiao-Shi
authors.initials: XS
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D063646:Carcinogenesis / Q000235:genetics*; D056905:Chromosome Breakpoints; D005260:Female; D015321:Gene Rearrangement; D060005:Genotyping Techniques; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D013058:Mass Spectrometry; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK break point; acral; melanoma; mucosal; mutation