人乳腺癌组织中p53基因单核苷酸多态性位点变异的研究

目的 观察乳腺癌患者p53基因的单核苷酸多态性位点(SNPs)变异,探讨p53基因在乳腺癌癌基因学中的意义.方法 选取p53基因位于外显子及内含子的共3对引物,利用SSCP(单链多肽构象)分析方法对30例乳腺癌样品进行分析及DNA测序.结果 在检测的30例乳腺癌组织样品中,p53基因在第一内含子和第七内含子中共有4个碱基替换被检测出,其中3个为Hapmap(Hapolotype Map Project,国际单倍型图谱计划)中已公布的SNP位点,另外1个从未被确认.在p53第7内含子位置处发现一高突变率(20%)的G→A(rs12947788)类型基因替换,在其上游20个碱基位置处存在另一已知高突变率的SNP位点A→C(rs12951053),此两者联合出现,在所检测的30例乳腺癌组织样本中共发现6例,占所检测标本的20%.结论 p53基因的SNPs分析对乳腺癌的早期发现、治疗和预后有一定意义.

p53 gene mutation in human breast cancer tissues

Objective To investigate the possible implication of the substitution at single Nucleotide Polymorphisms (SNPs) sites in p53 genes in the carcinogenesis of breast cancer. Methods The SNPs in p53 gene regions from 30 patients with breast cancer were analyzed by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and subsequent DNA sequencing. Results The totally 4 nucleotide substittution sites at the regions of intron 1 and intron 7 of p53 detected were found in 30 cases of breat cancer, which involved 3 published SNPs sites and 1 uncharacterized site. Among these substitutions, a G →A (rs12947788) mutation which occurred at the intron 7 was coupled with the cystidine nucleotide at a SNPs site A→C (rs12951053) of 20th nucleotide at its upstream, which occupied 20% of the breast cancer patients, implicaing the significance of the coupling of these two sites in the carcinogenesis of the breast cancer. Conclusion The DNA substitution analysis at the SNPs sites of p53 may serve as a helpful tool for the early diagnosis of breast cancer.