Díez Orland, Osorio Ana, Durán Mercedes, Martinez-Ferrandis José Ignacio, de la Hoya Miguel, Salazar Raquel, Vega Ana, Campos Berta, Rodríguez-López Raquel, Velasco Eladio, Chaves Javier, Díaz-Rubio Eduardo, Jesús Cruz Juan, Torres María, Esteban Eva, Cervantes Andrés, Alonso Carmen, San Román Juan Manuel, González-Sarmiento Rogelio, Miner Cristina, Carracedo Angel, Eugenia Armengod María, Caldés Trinidad, Benítez Javier, Baiget Montserrat
Servei de Genètica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Hum Mutat. 2003 Oct;22(4):301-12. doi: 10.1002/humu.10260.
We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ-line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site-specific female breast cancer families (15.4%). Of the families with male breast cancer cases, 59.1% presented mutations in the BRCA2 gene. We found a higher frequency of ovarian cancer associated with mutations localized in the 5' end of the BRCA1 gene, but there was no association between the prevalence of this type of cancer and mutations situated in the ovarian cancer cluster region (OCCR) region of exon 11 of the BRCA2 gene. The mutations 187_188delAG, 330A>G, 5236G>A, 5242C>A, and 589_590del (numbered after GenBank U14680) account for 46.6% of BRCA1 detected mutations whereas 3036_3039del, 6857_6858del, 9254_9258del, and 9538_9539del (numbered after GenBank U43746) account for 56.6% of the BRCA2 mutations. The BRCA1 330A>G has a Galician origin (northwest Spain), and BRCA2 6857_6858del and 9254_9258del probably originated in Catalonia (northeast Spain). Knowledge of the spectrum of mutations and their geographical distribution in Spain will allow a more effective detection strategy in countries with large Spanish populations.
我们对来自410个西班牙乳腺癌/卵巢癌家族的索引病例以及214例乳腺癌患者（其中19例为男性）进行筛查，以检测BRCA1和BRCA2基因中的种系突变，采用的方法包括单链构象多态性分析（SSCP）、蛋白质截短试验（PTT）、恒定变性凝胶电泳（CSGE）、变性梯度凝胶电泳（DGGE）以及直接测序。我们在BRCA1基因中鉴定出60个突变，在BRCA2基因中鉴定出53个突变。在观察到的53个不同突变中，11个是新的，12个仅在西班牙家族中报道过（占41.5%）。这组家族中突变的发生率为26.3%，但在乳腺癌和卵巢癌家族中该比例更高（52.1%）。在特定部位的女性乳腺癌家族中发现的突变比例最低（15.4%）。在有男性乳腺癌病例的家族中，59.1%在BRCA2基因中存在突变。我们发现，与BRCA1基因5'端定位的突变相关的卵巢癌频率更高，但这种癌症的发生率与BRCA2基因第11外显子的卵巢癌簇区域（OCCR）中的突变之间没有关联。187_188delAG、330A>G、5236G>A、5242C>A和589_590del（根据GenBank U14680编号）这几个突变占检测到的BRCA1突变的46.6%，而3036_3039del、6857_6858del、9254_9258del和9538_9539del（根据GenBank U43746编号）占BRCA2突变的56.6%。BRCA1基因的330A>G突变起源于加利西亚（西班牙西北部），BRCA2基因的6857_6858del和9254_9258del突变可能起源于加泰罗尼亚（西班牙东北部）。了解西班牙的突变谱及其地理分布，将有助于在有大量西班牙裔人口的国家制定更有效的检测策略。
