De Silva Wasanthi, Karunanayake Eric H, Tennekoon Kamani H, Allen Marie, Amarasinghe Indrani, Angunawala Preethika, Ziard Mohamed H
Institute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.
BMC Cancer. 2008 Jul 29;8:214. doi: 10.1186/1471-2407-8-214.
Breast Cancer is the most commonly diagnosed cancer among Sri Lankan women. Germline mutations in the susceptibility genes BRCA1 and BRCA2 in hereditary breast/ovarian cancer, though low in prevalence, are highly penetrant and show geographical variations. There have been only a few reports from Asia on mutations in BRCA1/2 genes and none from Sri Lanka.
A total of 130 patients with (N = 66) and without (N = 64) a family history of breast cancer, 70 unaffected individuals with a family history of breast cancer and 40 control subjects were analysed for BRCA1 mutations. All but exon 11 were screened by single strand conformation analysis (SSCP) and heteroduplex analysis. PCR products which showed abnormal patterns in SSCP were sequenced. Exon 11 was directly sequenced.
Nineteen sequence variants were found in BRCA1 gene. Two novel deleterious frame-shift mutations; c.3086delT/exon11 (in one patient) and c.5404delG/exon21 (in one patient and two of her family members) were identified. A possibly pathogenic novel missense mutation (c.856T>G/exon 11) and three novel intronic variants (IVS7+36C>T, IVS7+41C>T, IVS7+49del15) were characterised. Ten previously reported common polymorphisms and three previously reported intronic variants were also observed.
After screening of 66 patients with family history and 64 sporadic breast cancer patients, 2 deleterious mutations (c.3086delT and c.5404delG) in two families were identified and two more possibly pathogenic mutations (c.856T>G and IVS17-2A>T) in two families were identified.
BRCA1--Gene Bank: Accession # U14680 Version # 14680.1.
乳腺癌是斯里兰卡女性中最常被诊断出的癌症。遗传性乳腺癌/卵巢癌易感基因BRCA1和BRCA2中的种系突变，虽然患病率较低，但具有高度的外显率且存在地理差异。亚洲关于BRCA1/2基因突变的报道很少，斯里兰卡尚无相关报道。
对130例有（N = 66）和无（N = 64）乳腺癌家族史的患者、70例有乳腺癌家族史的未患病个体以及40例对照受试者进行BRCA1突变分析。除第11外显子外，其余均通过单链构象分析（SSCP）和异源双链分析进行筛查。在SSCP中显示异常模式的PCR产物进行测序。第11外显子直接测序。
在BRCA1基因中发现了19个序列变异。鉴定出两个新的有害移码突变；c.3086delT/第11外显子（1例患者）和c.5404delG/第21外显子（1例患者及其两名家庭成员）。表征了一个可能致病的新错义突变（c.856T>G/第11外显子）和三个新的内含子变异（IVS7+36C>T、IVS7+41C>T、IVS7+49del15）。还观察到10个先前报道的常见多态性和3个先前报道的内含子变异。
在筛查了66例有家族史的患者和64例散发性乳腺癌患者后，在两个家族中鉴定出2个有害突变（c.3086delT和c.5404delG），在另外两个家族中鉴定出另外两个可能致病的突变（c.856T>G和IVS17-2A>T）。
BRCA1——基因库：登录号#U14680版本#14680.1。
