他莫昔芬介导的绝经期子宫内膜pten基因突变的检测

摘要

目的 探讨绝经期服用他莫昔芬( tamoxifen,TAM)的乳腺癌患者子宫内膜中磷酸酶-张力蛋白(phosphatase and tensin,PTEN)基因突变与TAM介导的子宫内膜病变发生发展的关系.方法 应用聚合酶链反应-单链构象多态性(PCRSSCP)及DNA双向测序法分别检测服用TAM的绝经期患者、绝经期子宫内膜癌患者及绝经期子宫脱垂患者(正常子宫内膜)的pten基因9个外显子的突变情况.结果 在服用他莫昔芬组检测到4例pten基因突变,突变率为12.12％(4/33);在子宫内膜癌组检测到5例突变,突变率为22.72％ (5/22)；在正常子宫内膜组未检测到突变(0/20).TAM组与子宫内膜癌组及正常子宫内膜组突变率相比差异无统计学意义(P均＞0.05)；子宫内膜癌组与正常子宫内膜组比较,pten基因的突变率差异有统计学意义(P =0.049).结论 pten基因突变在TAM介导的子宫内膜病变的发生发展中可能起重要作用.%Objective To investigate the influence of tamoxifen on the postmenopausal women and test an assumption whether tamoxifen can cause the endometrial cancer by pten. Methods With PCR-SSCP method, sequence analysis and RT-PCR method, the authors examined the correlation of pten mutation of nine exons in endometrium of postmenopausal women with breast cancer who were taking tamoxifen . Results PCR-SSCP of pten and sequence analysis showed that 4/33 cases (12. 12% ) of tamoxifen group and 5/22 cases (22.72% ) of endometrial carcinoma group had mutation. There was no mutation in normal endometrium group. The differences of pten mutation rate was not significant between tamoxifen and carcinoma groups, and between tamoxifen and normal endometrium groups, but was significant between endometrial carcinoma and normal endometrium groups. Conclusion Pten gene mutation may be a diagnostic biomarker for the early event leading to the cancer.