乳腺导管内增生性病变p35外显子突变的研究

 目的肿瘤抑制基因突变是浸润性乳腺癌发生发展中常见事件，而其与包括普通型增生（UDH），不典型增生（ADH）及导管内原位癌（DCIS）的乳腺导管内增生性病变关系不明。探讨在乳腺导管内增生性病变的外显子突变情况，以期了解突变在乳腺癌发生发展中的作用。方法用高分辨率熔解曲线和测序研究122 例乳腺导管内增生性病变中外显子5~8 的突变情况。结果经HRM筛选，14 例患者DNA熔解曲线与野生型标准品熔解曲线大于阈值，经测序分析，其中13例出现外显子突变。35例UDH 中均未发现突变，10.7%（6/56）ADH 和22.6%（7/31）DCIS 发现至少1 个位点的点突变，其中1 例DCIS 发现2 个位点的突变。结论突变发生于乳腺导管内增生性病变中的ADH与DCIS，其可能为乳腺癌发生发展中的早期事件。

Mutation of p53 Exon in Breast Intraductal Proliferative Lesions

Objective Although mutation is one of the most common alterations identified in invasive breast carcinomas，it is not clear whether its alteration frequently occurs in intraductal proliferative lesions including usual ductal hyperplasia（UDH），atypical ductal hyperpla-sia（ADH）and ductal carcinoma in situ（DCIS）. The aim of this study is to investigate the mutation in intraductal proliferative lesions，and clarify its significance in breast carcinogenesis. Methods p53 mutation was examined in 122 cases of noninvasive breast lesions in-cluding UDH，ADH and DCIS by high-resolution melting（HRM），followed by DNA sequence. Results The positive rates of mutation were 0.0%，10.7% and 22.6% in UDH，ADH and DCIS，respectively. Conclusion p53mutation occurs in intraductal proliferative lesions including ADH and DCIS，and might be an early event in breast carcinogenesis.