中国134例黑色素瘤患者P16^(INK4a)、CDK4和CCND1基因突变及其临床意义  

Mutations of P16^(INK4a)/CDK4/CCND1 genes in 134 Chinese melanoma patients and their clinical significance

作　　者：吴晓雯 闫君雅 代杰[1] 孔燕[1] 郭军[1] 

机构地区：[1]北京大学肿瘤医院肾癌黑色素瘤内科,北京100142

出　　处：《基础医学与临床》2018年第2期153-157,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81672696;81402264);北京市自然科学基金(7154187;7152033);北京市百千万人才工程(20140000212232K26)

摘　　要：目的通过分析中国黑色素瘤患者P16^(INK4a)、CDK4和CCND1基因的突变情况,探索其可能的临床意义。方法研究共纳入2010年1月至2014年12月在北京肿瘤医院就诊的134例中国黑色素瘤患者,收集其肿瘤组织切片(肢端型37例,黏膜型87例,非肢端皮肤型10例),通过PCR扩增及Sanger测序,检测P16^(INK4a)、CDK4和CCND1基因突变情况,并分析基因突变情况与临床预后的相关性。结果 134例黑色素瘤患者P16^(INK4a)、CDK4和CCND1基因突变率分别为8.2%(11/134)、0.75%(1/134)和0%(0/134)。81.8%(9/11)的P16^(INK4a)基因突变可能影响蛋白质功能。P16^(INK4a)野生型患者的总生存期明显长于突变型患者(χ~2=8.872,P<0.01)。P16^(INK4a)基因突变是影响黑色素瘤的独立预后因素(P<0.05)。结论 P16^(INK4a)基因可能成为黑色素瘤靶向治疗新的突破点。Objective To investigate the frequency of P16^INK4a,CDK4 and CCND1 gene mutations in Chinese melanoma patients and to find out the potential clinical significance. Methods The samples in this study were collected from 134 melanoma patients（ 37 acral melanomas,87 mucosal melanomas,10 non-acral skin melanomas）,hospitalized in Beijing Cancer Hospital from January 2010 to December 2014.The mutation status of P16^INK4a,CDK4 and CCND1 was detected by PCR amplification and Sanger sequence. Statistical analyses were used to investigate the correlation between gene mutation and prognosis. Results Among 134 samples,the mutation frequency of P16^INK4a,CDK4,CCND1 was 8. 2%（ 11/134）,0. 75%（ 1/134）,0%（ 0/134） respectively. 81. 8%（ 9/11） of the P16^INK4agene mutation may affect protein function.The median survival time of melanoma patients with P16^INK4a mutations was significantly shorter than the patients without P16^（INK4a mutations（ χ^2= 8. 872,P〈0. 01）. P16^（INK4a）gene mutation was an independent prognostic factor for melanoma（ P〈0. 05）. Conclusions P16^INK4a may be a breaking point of targeted therapy for melanoma.

关 键 词：黑色素瘤 P16^INK4A CDK4 CCND1 基因突变 

分 类 号：R739.5[医药卫生—肿瘤]