卵巢上皮性癌p53基因突变的检测和序列分析.docVIP

卵巢上皮性癌p53基因突变的检测和序列分析 中华妇产科杂志 1998年第3期第0卷 论著 作者：关新　郎景和　卞美璐　单建军　关钧　范慕贞 单位：100029 北京，中日友好医院妇产科(关新、卞美璐)，临床研究所生化室(关钧、范慕贞)；北京协和医院妇产科(郎景和)；吉林炭素厂职工医院妇产科(单建军) 关键词：卵巢肿瘤；基因；p53；突变；聚合酶链反应 　　【摘要】　目的　了解卵巢上皮性癌p53基因突变的特点及其与临床分期的关系。方法　采用聚合酶链反应-单链构象多态性检测(PCR-SSCP)和序列分析的方法对46例卵巢上皮性癌进行外显子5、6、7突变的检测和分析。结果　p53基因突变8例并得到证实。包括8个点突变(6个错义突变，1个静息突变和1个内含子突变)和1个碱基对插入突变(在下游产生终止信号)。突变中碱基转换突变占总突变的88.9%(8/9)，并以G→A的转换突变为主，占转换突变的87.5%(7/8)。175、245位密码子的突变占总突变的62.5%。临床Ⅰ、Ⅱ期的突变率为20.0%，临床Ⅲ、Ⅳ期为16.7%，差异无显著性(P＞0.05)。结论　卵巢上皮性癌p53基因突变是自发性突变，是由于DNA合成和修复过程中的随机错误所致。175与245位密码子可能是卵巢上皮性癌p53基因突变的主要位点。p53基因突变与临床分期无关，故认为p53基因突变于卵巢癌早期就有所发生，并持续于肿瘤发展的全过程。 　　Detection and Sequence Analysis of the p53 Gene Mutation in Epithelial Ovarian Cancer　Guan Xin, Lang jinghe, Bian Meilu, et al. China-Japan Friendship Hospital, Beijing 100029 　　【Abstract】　Objective　To find thd characteristics of p53 gene mutation in epithelial ovarian cancer and to analyze the relationship between p53 mutation and FIGO stage. Methods　p53 mutations in exon 5 to 7 were detected by single-strand conformational polymorphism (SSCP) and sequencing technique. Results　8 of 46 tumor tissues demonstrated a SSCP band shift in the region of the gene. All of them have been characterized to represent DNA alterations by sequencing, including 8 point mutations (6 missence, 1 silent mutation and 1 in intron) and a 1-base pair insertion (introducing a stop codon downstream). Overall, 88.9% of mutation were transitions, and most of them are G→A transitions (7/8, 87.5%). 62.5% of the mutation were found in 175 and 245 codon. The percentage of the mutation in stage Ⅰ and stage Ⅱ was 20.0%, and in stage Ⅲ and stage Ⅳ was 16.7% (P＞0.05). Conclusion　The arising of p53 mutations in ovarian cancer is due to spontaneous error in DNA synthesis and repair. Codon 175, 245 are the two mutational hot spots. There is no relationship between the mutation of p53 gene and FIGO stage in epithelial ovarian cancer. 　　【Key words】　Ovarian neoplasms　　Genes, p53　　Mutation　　Polymerase chain r