BRCAl基因突变与年轻患者乳腺癌发生的相关性分析

目的 筛查年轻乳腺癌BRCAl基因的突变位点及SNP携带情况,探讨BRCAl基因突变与年轻乳腺癌发生的关系.方法 来自我院2004年1月-2006年8月收集的乳腺癌组织共30例,其中5例有至少1个一级亲属患乳腺癌,发病年龄≤35岁.由乳腺癌组织提取基因组DNA,对BRCAl基因第2、11C、11F、11L、11I、16、20外显子的编码序列进行PCR扩增.扩增产物进行DNA直接测序证实,利用DNA Star-MagAlign软件进行序列比较.结果 BRCAl基因中共发现14个序列变异,有3个移码突变(cDNA2639、2640delTA、3343delG及3398delT)和11个点突变(cDNA 2570 C>T、cDNA2620 A>T、1473A>G、1561C>T、1594G>A、2206A>G、2227T>C、2659C>A、2806T>C、3307A>G、3375G>A),其中3个乳腺癌家族史阳性.突变率为10%(3/30).第16及20外显子未发现突变.结论 BRCAl突变主要位于第11号外显子上,乳腺癌家族史阳性的年轻乳腺癌突变率高,3个移码突变可能与年轻乳腺癌发生相关.

Relationship between mutation of BRCA1 and susceptibility to early onset of breast cancer

Objective To detect the prevalence of Breast Cancer Susceptibility Gene 1 (BRCA1) mutations and single nucleotide polymorphism (SNP) among young patients with breast cancer and to study the relationship between BRCAI gene mutation and susceptibility to breast cancer. Methods 30 samples of breast cancer tissue were collected from female patients with breast cancer diagnosed when they were aged 35 5 of which had at least one first-degree relative affected with breast cancer. Genomic DNA was extracted from the breast cancer tissues. The PCR products were amplified in the coding sequence of exon 2, 11C, 11F, 11L, 11I, 16, and 20 by using polymerase chain reaction. Then the PCR products were analyzed using DNA direct sequencing. The sequence was compared with the DNA Star-MagAlign software. Results A total of 14 sequence variations in BRCA1 gene were identified, including 3 frameshift mutations (cDNA2639, 2640delTA, 3343 delG, and 3398delT) and 11 spot mutations (cDNA 2570 C > T , cDNA 2620 A>T, 1473 A>G, 1561 C>T, 1594G >A, 2206 A>G, 2227 T>C, 2659 C>A, 2806T > C, 3307 A >G, and 3375 G > A). Three patients with these mutations had a family history of breast cancer. The mutation frequency of BRCA1 was 10% (3/30). No mutation was found in the exons 16 and 20. Conclusion Patients with breast cancer aged ≤35 have BRCA1 mutations located in the exon 11 mainly. The mutation frequency of the breast cancer patients aged ≤ 35 with breast cancer family history is higher than those without family history. Three frameshift mutation sites may be related to early onset of breast cancer.