Molecular Medicine, Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Thane Belapur Road, Rabale, Navi Mumbai, 400701, India.
Med Oncol. 2012 Dec;29(5):3272-81. doi: 10.1007/s12032-012-0294-9. Epub 2012 Jul 3.
We examined BRCA1/2 mutations and single nucleotide polymorphisms (SNPs) for identification of BRCA1 haplotypes, in early-onset breast cancer patients and their relatives, sporadic breast cancer patients, and unrelated normal healthy females, of Indian ethnicity. Peripheral blood DNA was amplified by polymerase chain reaction, at BRCA1/2 coding exons and subject to nucleotide sequencing using ABI 3100 Genetic Analyzer. We observed BRCA1/BRCA2 mutations in 52 % early-onset breast cancer patients and in 57 % relatives. Deleterious mutations detected in early-onset patients and relatives were 187delAG, 632insT, 1052delT, Q759X, Q780X, R1203X, 5154delC, IVS14 + 1G > A, IVS17 + 1G > T, and 632insT in BRCA1 gene; and 4075delGT, 5076delAA, 6079delAGTT, and W3127X in BRCA2 gene. A high degree of penetrance of BRCA1/2 gene mutations was observed in the relatives. BRCA1/2 SNPs were identified in the Indian population, and association of BRCA1 haplotypes with breast cancer was investigated. A significantly increased frequency of the SNPs 203G/A, 3624A/G and 7470A/G SNPs in BRCA2 gene was observed in normal controls indicative of a protective effect of the SNPs. BRCA1 haplotype 2 was most frequently observed in our population. Our study indicates a high incidence of BRCA1/BRCA2 gene mutations in the Indian patients. The BRCA1/2 mutations and SNPs are detailed on our website http://relibrca.rellife.com .
我们研究了 BRCA1/2 基因突变和单核苷酸多态性（SNP），以鉴定 BRCA1 单倍型，包括早发性乳腺癌患者及其亲属、散发性乳腺癌患者和无关的正常健康女性，均为印度裔。通过聚合酶链反应扩增外周血 DNA，在 BRCA1/2 编码外显子上进行核苷酸测序，并使用 ABI 3100 遗传分析仪进行。我们在 52%的早发性乳腺癌患者和 57%的亲属中观察到 BRCA1/BRCA2 突变。在早发性患者和亲属中检测到的有害突变包括 187delAG、632insT、1052delT、Q759X、Q780X、R1203X、5154delC、IVS14 + 1G > A、IVS17 + 1G > T 和 632insT 在 BRCA1 基因中；以及 4075delGT、5076delAA、6079delAGTT 和 W3127X 在 BRCA2 基因中。在亲属中观察到 BRCA1/2 基因突变的高度外显率。在印度人群中鉴定了 BRCA1/2 SNP，并研究了 BRCA1 单倍型与乳腺癌的关系。在正常对照组中观察到 BRCA2 基因中的 SNP 203G/A、3624A/G 和 7470A/G 频率显著增加，提示 SNP 具有保护作用。在我们的人群中，BRCA1 单倍型 2 观察到的频率最高。我们的研究表明，印度患者中 BRCA1/BRCA2 基因突变的发生率很高。BRCA1/2 突变和 SNP 已详细记录在我们的网站 http://relibrca.rellife.com 上。
