CAJ | 학술논문

目的探讨中国老年黑色素瘤患者的基因突变情况以及与临床特点和预后的关系.方法用PCR扩增和直接测序法检测黑色素瘤中常见的突变基因KIT、BRAF和NRAS在中国老年恶性黑色素瘤患者肿瘤组织中的突变情况,并对基因突变和临床特点、预后的关系进行统计分析.结果 122例老年黑色素瘤患者中,最常见的病理亚型为肢端及黏膜型.总的中位生存时间为53.0个月.KIT基因的突变率为13.9％,其中最常见的突变类型为11号外显子L576P(4例).BRAF基因的突变率为18.0％,其中86.0％为V600E突变,非慢性日光损伤型老年患者的BRAF基因突变率明显增高(85.7％,P＜0.05).NRAS基因的突变率为7.4％,Q61K为最常见突变类型.KIT突变患者的生存时间明显少于野生型患者(33.0个月和55.0个月,P=0.017). 结论 KIT突变是中国老年黑色素瘤患者预后不良因素.KIT和BRAF基因突变在老年黑色素瘤患者中较为常见,这为KIT和BRAF抑制剂在老年黑色素瘤患者中的个体化靶向治疗提供了初步的理论依据.
목적 탐토중국노년흑색소류환자적기인돌변정황이급여림상특점화예후적관계.방법 용PCR확증화직접측서법검측흑색소류중상견적돌변기인KIT、BRAF화NRAS재중국노년악성흑색소류환자종류조직중적돌변정황,병대기인돌변화림상특점、예후적관계진행통계분석.결과 122례노년흑색소류환자중,최상견적병리아형위지단급점막형.총적중위생존시간위53.0개월.KIT기인적돌변솔위13.9％,기중최상견적돌변류형위11호외현자L576P(4례).BRAF기인적돌변솔위18.0％,기중86.0％위V600E돌변,비만성일광손상형노년환자적BRAF기인돌변솔명현증고(85.7％,P＜0.05).NRAS기인적돌변솔위7.4％,Q61K위최상견돌변류형.KIT돌변환자적생존시간명현소우야생형환자(33.0개월화55.0개월,P=0.017). 결론 KIT돌변시중국노년흑색소류환자예후불량인소.KIT화BRAF기인돌변재노년흑색소류환자중교위상견,저위KIT화BRAF억제제재노년흑색소류환자중적개체화파향치료제공료초보적이론의거.
Objective To investigate the gene mutation status in Chinese elderly patients with melanoma and to explore the correlation of gene mutation with clinical characteristics and prognosis.Methods Melanoma tissue samples from Chinese elderly patients were analyzed for gene mutations of KIT,BRAF and NRAS in genomic DNA by polymerase chain reaction(PCR) amplification and Sanger sequencing.The correlations of gene mutations with clinicopathologic features and prognosis were statistically analyzed.Results The most common pathological subtypes were acral and mucosal among 122 elderly patients with melanoma.The median overall survival time was 53 months.Somatic mutation in the KIT gene was 13.9％,in which mutations exon 11 L576P mutation was the most common mutation type(4 cases).Mutation in the BRAF gene was 18.0％,in which V600E mutation was the most common mutation type(86.0％),and the incidence of BRAF mutation was increased in patients with non-chronic sun-damaged disease as compared with other subtypes(85.7％,P＜0.05).The mutation in the NRAS gene was 7.4％,in which Q61K mutation was the most common type.The survival time was shorter in patients with KIT mutation than in patients with wild type KIT gene(33.0 months vs.55.0 months,P＜0.05).Conclusions KIT mutation is an adverse prognostic factor for Chinese elderly patients with melanoma.KIT and BRAF gene mutations are frequent in elderly patients with melanoma,which provides a preliminary theoretical basis for individualized targeted therapy with KIT and BRAF inhibitors in elderly patients with melanoma.