肿瘤相关ACTR基因多聚谷氨酰胺通道的编码序列多态性分析

目的：研究ACTR基因(甲状腺激素受体和视黄醛激活因子activator of retinoid and thyroid receptors，或称乳腺癌扩增基因)中多聚谷氨酰胺通道编码序列多态性与乳腺癌之间的关系。方法：107个DNA样本来自乳腺癌细胞系、原发性乳腺癌、BRCA1／BRCA2突变携带者外周血和正常对照人群外周血，应用PCR克隆／测序方法鉴别个体的每一种特异poly Q编码序列。结果：共发现23种特异的poly Q编码序列，肿瘤细胞系和原发性肿瘤组中拥有超过两个特异poly O编码序列的个体比例明显高于正常对照组人群；肿瘤细胞系和原发性肿瘤组中拥有罕见poly Q编码序列的个体比例亦明显高于正常对照组人群，原发性肿瘤组中拥有至少一个小于27个poly Q重复序列的个体比例明显高于BRCA1／BRCA2突变携带者组。结论：本结果提示ACTR基因的poly O编码序列的在体不稳定性可能作用于乳腺癌的致病过程。

Analysis of polymorphic poly glutamine encoding sequences in tumor related to ACTR gene

Objective To study the relationship between the polymorphic poly Q encoding sequences of ACTR gene and breast cancer risk. Methods The polymorphic poly Q encoding sequences of ACTR gene from 107 DNA samples, including breast cancer cell lines, sporadic primary breast tumors, and blood samples from BRCA1/BRCA2 mutation carriers and the general population, were resolved by PCR/cloning and sequencing of each individual clone. Results Twenty three distinct poly Q encoding sequence patterns were found. Significantly higher proportion of the tumor cell lines and primary tumors have more than 2 distinct sequence patterns encoding the poly Q tract when compared to general population. Similarly, significantly higher proportion of cancer cell lines or primary breast tumors contained rare sequence patterns when compared to general population. Statistical analysis revealed that the proportion of women having at least one allele 27 repeats in sporadic breast cancer is significantly higher than that in BRCA1/BRCA2 mutation carriers or general population. Conclusion Our results suggest that somatic instability of the poly Q encoding region may contribute to the role of ACTR gene in the tumorigenesis of breast cancer.