关键词: 黑色素瘤, 少数民族, DNA突变分析, 临床特征

Abstract: 【Abstract】 Objective To investigate associations between clinicopathological characteristics and mutations in susceptibility genes in cutaneous melanoma （CMM）. Methods A total of 94 patients with confirmed CMM were collected from People′s Hospital of Xinjiang Uygur Autonomous Region from January to December in 2019, and their clinical and histopathological characteristics were retrospectively analyzed. In 48 paraffin-embedded melanoma tissue specimens, Sanger sequencing was performed to detect mutations in the BRAF, NRAS, c-KIT genes and the promoter region of human telomerase reverse transcriptase （hTERT） gene, and the association between gene mutations and clinicopathological characteristics was analyzed. Measurement data were compared using t test, and enumeration data were compared using chi-square test or Fisher′s exact test. Results Among the 94 patients with CMM, there were 46 （48.9%） males and 48 （51.1%） females, with the age being 58.5 ± 16.0 years; 41（43.6%） patients were of Han nationality, and 53 （56.4%） were of ethnic minorities. Skin lesions were located at the acral sites in 50（53.2%） patients, including 27 （28.7%） of Han nationality; non-acral skin lesions occurred in 44 （46.8%）, including 14 （31.8%） of Han nationality; there was a significant difference in the nationality distribution between the acral CMM group and non-acral CMM group（χ2 = 5.25, P = 0.022）. Histopathological examination showed CMM of Clark grades Ⅳ orⅤ in 41 （43.6%） cases, ulcers in 52 （55.3%） cases, and lymph node metastasis in 32 （34.04%） cases at the first clinic visit. Gene sequencing revealed BRAF gene mutations in 11 （22.9%） of 48 cases, including c.1799 T>A（p.V600E）, c.1790 T>A（p.L597Q） and c.1394 C>T（p.S465F）; NRAS gene mutation c.182 A>G（p.Q61R）was identified in 5 （10.4%） cases; c-KIT gene mutations were identified in 6 （12.5%） cases, including c.1727 T>C（p.L576P） and c.1669 T>C（p.W557R）; mutations in the promoter region of hTERT gene were identified in 7 （14.6%） cases, including 4 cases with a mutation at 124 bp upstream of the ATG start codon （C228T） and 3 cases with a mutation at 146 bp upstream of the ATG start codon （C250T）. Among 26 patients aged < 60 years, BRAF gene mutations were found in 9, and the incidence of BRAF gene mutations was significantly higher in the patients aged < 60 years than in those aged ≥ 60 years （2/22, P < 0.05）, but significantly lower in the patients with acral CMM （3/27） than in those with non-acral CMM （8/21, P < 0.05）; the incidences of the NRAS, c-KIT and hTERT gene mutations were all significantly higher in the patients with lymph node metastases （3/10, 4/10, 4/10, respectively） than in those without （2/38, 2/38, 3/38, respectively, all P < 0.05）. Conclusion CMM lesion locations significantly differed among different ethnic groups; the BRAF gene mutation was associated with the age of patients and lesion locations of CMM; NRAS, c-KIT gene mutations and hTERT promoter mutations were closely related to lymph node metastasis.

Key words: Melanoma, Minority groups, DNA mutational analysis, Clinical features