乳腺癌患者高频BRCA1等位基因研究

A highly frequent BRCA1 allele in Chinese patients with breast cancer

目的观察乳腺癌患者BRCA1基因变异。方法测序分析35例乳腺癌患者和10名正常女性BRCA1基因的全长第11外显子共3427bp,然后与GeneBank记录的BRCA1正常序列比较。结果35名患者中11名(31.4%)存在2处同义突变:2201C>T、2430T>C,和3处误义突变:2731C>T、3232A>G、3667A>G(EMBL/GeneBank/DDBJ基因记录号AY304547),分别造成第871、1038和1183位氨基酸发生替换(蛋白质记录号AAP70031);10例患者和6名正常个体的基因序列与正常BRCA1基因完全相同;另14名患者以及4名健康个体为上述突变基因与正常基因的杂合体:2201、2430和2731位为碱基C/T杂合,3232和3667位A/G杂合。结论乳腺癌患者突变等位基因纯合体的比率明显高于正常人,提示该等位基因纯合体可能与中国人乳腺癌发病存在关联。

Objective To observe the mutation of BRCA1 gene in the paitents with breast cancer.Methods The whole length of exon 11 of BRCA1 (3427 bp) was amplified with two pairs of primers in 35 patients with breast cancer and 10 nomral women.The amplicons were then submitted to direct sequencing.Results Five polymorphisms were identified in 11 patients (31.4%, 11/35):2201C>T,2430T>C,2731C>T,3232A>G and 3667A>G (EMBL/Gene Bank/DDBJ AY304547).Ten patients and 6 donors possessed identical sequence as normal BRCA1 mRNA,and the rest 14 patients and 4 donors were heterozygote of the mutated allele (BRCA1-2201T2430C2731T3232G3667G) and normal BRCA1.Conclusion The frequency of the mutated allele in breast cancer patients is much higher than that in female controls,suggesting that the homozygote of this allele may implicate a disease-association in Chinese population.