【作者】 张磊；

【导师】 曹明智； 吴琍；

【作者基本信息】 青岛大学 ， 普通外科学， 2009， 硕士

【摘要】 目的:乳腺癌是危害妇女健康的主要恶性肿瘤之一。乳腺癌易感基因BRCA1(breast cancer gene 1)是近年来发现的一种与乳腺癌密切相关的抑癌基因。国内外其他人群已进行了大量研究发现相关的基础突变,并应用于早期普查和早期预防性干预。本研究拟应用PCR及DNA直接测序的方法研究青岛地区55例家族性及早发性乳腺癌中BRCA1基因外显子2、20的突变情况及突变位置,探讨其与乳腺癌发病的关系。方法:选择符合条件的家族性及早发性乳腺癌患者55例为实验组,提取石蜡标本DNA,设计2对引物对BRCA1基因第2、20外显子进行扩增,应用PCR技术和DNA直接测序技术检测所有标本BRCA1基因外显子2、20的突变情况。结果:55例乳腺癌患者在BRCA1基因第2外显子上发现1例(1.8%)致病性突变(176G＞C),此例患者为家族性乳腺癌患者,其在30例家族性乳腺癌患者中,突变率为3.3%(1/30)。而55例家族性及早发性乳腺癌在外显子20上未发现任何致病性突变。结论:BRCA1基因外显子2的序列突变与青岛地区家族性乳腺癌的发生有密切关系,而BRCA1基因外显子2、20的序列突变对青岛地区早发性乳腺癌影响不大,有待于寻找BRCA1基因其他位置的突变位点。更多还原

【Abstract】 Objective Breast cancer is one of the most common malignancy among women.BRCA1(breast cancer gene 1) is the tumor suppressor genes that most closely related to breast cancer.At present foreign and domestic other groups have conducted extensive research and found some founder mutations,which benifit in early census and early preventive intervention. On this study we detect the mutation sites of BRCA1 gene exon2 and exon20 in familial breast cancer and early-onset breast cancer in Qingdao and to study the relationship between BRCA1 gene mutation and breast cancer.Methods Fifty-five familial and/or early-onset breast cancer patients from unrelated families were analyzed.Genomic DNA were collected from paraffin-embedded specimens.Two pairs of primers were designed for the PCR amplications on exon 2 and exon 20 of BRCA1.The partial exons(2,20) of BRCA1 gene in 55 breast cancer patients were analyzed by polymerase chain reaction(PCR) and direct DNA sequencing.Results One kind of disease-related mutation on the exon 2 of the BRCA1 gene(176 G＞C) was found in one unrelated family,the mutation rate is 1.8% (1/55).The case was a familial breast cancer patient,so the mutation rate was 3.3%(1/30) in familial breast cancer patients.No pathogenic mutation was found on the exon 20 of the BRCA1 gene in 55 cases of breast cancer.Conclusions The mutation on the exon 2 of the BRCA1 is involved in carcinogenesis of the familial breast cancer,but the gene sequence of what we have studied on exon 2 and exon 20 of BRCA 1 doesn’t account much for occurrence of the early-onset breast cancer in Qingdao,China.It is important to find new mutations at the other gene loci in BRCA1 gene.更多还原