乳腺增生病p53基因第7外显子突变检测

Mutations in exon 7 of p53 gene in breast hyperpalsia

目的 探讨p5 3基因在乳腺癌发生早期的作用及早期诊断乳腺癌的分子病理指标。方法 用PCR SSCP法检测 36例乳腺单纯性增生、31例不典型增生、14例原位癌和 16例浸润癌中p5 3基因第 7外显子突变 ,并用DNA直接测序技术确定突变的碱基及其所在的密码子。结果 乳腺单纯性增生、不典型增生、原位癌、浸润癌中p5 3基因第 7外显子的突变率分别为 0 %、6 .5 % (2 /31)、2 1.4% (3/14)、18.8% (3/16 )。 8例突变中 ,3例发生于 2 5 1密码子 ,4例发生于 2 48密码子 ,1例发生于 2 36密码子。表现为碱基替换 (5例 )、缺失 (2例 )、插入 (1例 )共三种突变方式。并在 1例原位癌中首次发现了 2 5 1密码子的同义突变 (ATC→ATT ,异亮氨酸→异亮氨酸 )。结论 乳腺癌不典型增生中存在p5 3基因第 7外显子突变 ,该突变可能在乳腺不典型增生发展到乳腺癌的过程中起重要作用 。

Objective To investigate the role of p53 gene in the early stages of human breast carcinogenesis and index of early diagnosis of breast carcinomas. Methods 36 cases of epithelial hyperplasia of usual type,31 cases of atypical hyperplasia,14 cases of breast carcinomas in situ and 16 cases of breast invasive carcinomas were employed to detect exon 7 mutations of p53 gene by polymerase chain reaction single-strand conformational polymorphism(PCR-SSCP) and direct DNA sepencing. Results Mutations in exon 7 of p53 gene were found in 6.5%(2/31) of breast atypical hyperplasia,21.4%(3/14) of carcinomas in situ and 18.8%(3/16) of invasive carcinomas,which were in codon 251,codon 248,codon 236. A same sence mutation at codon 251(ATC→ATT) is seen in one case of carcinomas in situ.Exon 7 mutations was not observed in hyperplasia of usual type. Conclusions Exon 7 mutations of p53 gene is involved in breast atypical hyperplasia,which may play an important biological role in the development from atypical hyperplasia to breast cancer,may be an assistant index in early diagnosis of breast carcinoma.