Jara Lilian, Ampuero Sandra, Santibáñez Eudocia, Seccia Lorena, Rodríguez Juan, Lay-Son Mario Bustamante Guillermo, Ojeda José Manuel, Reyes José Miguel, Blanco Rafael
Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Santiago, Chile.
Biol Res. 2004;37(3):469-81. doi: 10.4067/s0716-97602004000300011.
BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G) and one variant of unknown significance (E1250K) were found in four of these families. Also, a new mutation (4185delCAAG) and one previously described polymorphism (E1038G) were found in two other families. The 185delAG was found in a 3.17% of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin.
BRCA1基因突变几乎存在于所有有早发性乳腺癌和（或）卵巢癌多例的家族中，约占遗传性乳腺癌的30%。尽管迄今为止已描述了1237种以上不同的突变、多态性和变体，但已发现该基因中有几种突变是反复出现的。我们分析了63个智利乳腺癌/卵巢癌家族中的18种常见BRCA1突变。利用错配PCR检测、等位基因特异性寡核苷酸杂交检测、限制性片段分析、等位基因特异性PCR检测和直接测序技术，对这些突变所在的5个外显子和2个内含子进行了分析。在其中4个家族中发现了2种BRCA1突变（185delAG和C61G）以及1种意义不明的变体（E1250K）。此外，在另外2个家族中发现了1种新突变（4185delCAAG）和1种先前描述的多态性（E1038G）。185delAG在3.17%的家族中被发现，其他突变仅在该队列的1个家族中出现。因此，这些突变在智利人群中并不突出。检测到的意义不明的变体和多态性可能代表了西班牙裔的奠基者效应。
