Llort Gemma, Muñoz Carmen Yagüe, Tuser Mercè Peris, Guillermo Ignacio Blanco, Lluch José Ramón Germà, Bale Allen E, Franco Mayra Alvarez
Unidad de Consejo Genético. Servicio de Prevención y Control del Cáncer, Instituto Catalonian National Cancer Institute, Barcelona, Spain.
Hum Mutat. 2002 Mar;19(3):307. doi: 10.1002/humu.9014.
BRCA1 and BRCA2 mutations underlie a substantial proportion of all hereditary breast cancer. The mutational spectrum in these genes is very broad, with hundreds of different BRCA mutations reported worldwide. However, high frequency founder mutations make up a substantial fraction of all mutations in some ethnic groups. We directly sequenced BRCA1 and BRCA2 in 35 Spanish breast/ovarian cancer families and found 13 mutations of which 3 had been reported previously in Spain. The ten novel mutations are: IVS5+1 G>A, 1491delA, Leu1086Ter, and Gln895Ter in BRCA1; Glu49Ter, 5373delGTAT, 5947delCTCT, 6672delTA, 8281insA, and Pro3039Leu (which also involves a splice site) in BRCA2. Our data, in combination with previous reports, indicate that 14 mutations have been seen recurrently in Spanish families. Analyzing these 14 mutations in 42 previously untested breast/ovarian cancer families revealed only two families testing positive, one for BRCA1 185delAG and one for BRCA2 9254delATCAT. While several mutations have been found recurrently in Spain, none appear to be high frequency founder mutations based on studies of breast and ovarian cancer families.
BRCA1和BRCA2基因的突变是所有遗传性乳腺癌的一大部分病因。这些基因的突变谱非常广泛，全球已报道了数百种不同的BRCA突变。然而，高频始祖突变在某些种族群体的所有突变中占很大比例。我们对35个西班牙乳腺癌/卵巢癌家系中的BRCA1和BRCA2进行了直接测序，发现了13种突变，其中3种此前已在西班牙报道过。这10种新突变分别是：BRCA1基因中的IVS5+1 G>A、1491delA、Leu1086Ter和Gln895Ter；BRCA2基因中的Glu49Ter、5373delGTAT、5947delCTCT、6672delTA、8281insA和Pro3039Leu（该突变也涉及一个剪接位点）。我们的数据与之前的报告相结合，表明在西班牙家系中已反复发现14种突变。对42个此前未检测的乳腺癌/卵巢癌家系中的这14种突变进行分析，仅发现两个家系检测呈阳性，一个家系携带BRCA1基因的185delAG突变，另一个家系携带BRCA2基因的9254delATCAT突变。虽然在西班牙已反复发现几种突变，但基于对乳腺癌和卵巢癌家系的研究，似乎没有一种是高频始祖突变。
