45例人前列腺癌雄激素受体基因B～H外显子的突变研究

Study on mutations of exon B～H of the androgen receptor gene in 45 cases of patients with prostate cancer

目的和方法 :为探讨雄激素受体 (AR)与前列腺癌 (PC)发生发展及内分泌治疗不敏感的关系 ,我们首先建立了用PC的穿刺和石蜡切片组织检测AR基因突变的PCR -SSCP(双链构象多态性 ) -双链DNA循环测序法。并用上述方法检测了 45例国人前列腺癌组织 (6例穿刺组织 ,39例石蜡切片 )AR基因B～H外显子的基因突变。结果 :在 6例患者的癌组织中证实有 7个SSCP泳动变位片段 (其中一患者有两个外显子异常 ) ,这 6例患者中 4例为低分化腺癌 ,其中 2例已有远处转移 ,而序列分析证实这 2例转移患者SSCP异常的外显子H片段各存在一错义突变 (Glu 872Gln、Met 886Ile)。这两种AR的基因突变国内外均未见报道 ,为在PC中新发现的突变。结论 :实验发现AR突变均发生在前列腺癌的中晚期 。

AIM and METHODS: To learn more about the mechanism of prostate cancer (PC) development and progression to androgen independence, the exons B～H of the androgen receptor (AR) gene of forty-five patients with prostate cancer, six puncture tissues and thirty-nine slide tissues, were analyzed by polymerase chain reaction-single strand conformation technique (PCR-SSCP). RESULTS: Seven abnormal mobility shifts were found in five patients by PCR-SSCP. Combining the method with direct DNA cycle sequencing, two distinct missense (Glu872Gln, Met886Ile) point mutations were identified in puncture tissues from two patients of advanced prostate cancer with distant metastasis. These two point mutations represented two novel mutations. CONCLUSION: AR gene mutations might play an important role in the development and progression of prostate cancer.