Jara Lilian, Ampuero Sandra, Santibáñez Eudocia, Seccia Lorena, Rodríguez Juan, Bustamante Mario, Martínez Víctor, Catenaccio Alejandra, Lay-Son Guillermo, Blanco Rafael, Reyes José Miguel
Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Av. Independencia 1027, Casilla 70061, Santiago, Chile.
Cancer Genet Cytogenet. 2006 Apr 1;166(1):36-45. doi: 10.1016/j.cancergencyto.2005.08.019.
A sample of 64 high-risk breast and/or ovarian cancer families from Chile were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIN no. 113705) and BRCA2 (MIN no. 600185) genes using conformation-sensitive gel electrophoresis, and the mutations found were confirmed with direct sequencing. Seven families (10.9%) were found to carry BRCA1 mutations and three families (4.7%) had BRCA2 mutations. Six different pathogenic mutations were detected in BRCA1, four that had been reported previously (c.187_188delAG; c.300T-->G, c.3450_3453delCAAG and IVS17-1G-->A) and two novel mutations (c.2605_2606delTT and c.4185_4188delCAAG). In BRCA2, we found three different pathogenic mutations, two previously described (c.6174delT and c.6503_6504delTT) and one novel mutation (c.5667delT). We also identified nine variants of unknown significance (five in BRCA1 and four in BRCA2). These findings indicate that the Chilean population has a heterogeneous spectrum of prevalent BRCA mutations. Given the results obtained in our study, the screening of the entire BRCA1 and BRCA2 coding regions is necessary for the molecular genetic testing of Chilean high-risk breast/ovarian cancer patients. To our knowledge, this is the first genetic study of BRCA gene mutations conducted in Chile. The Chilean population has a well-known admixed Amerindian-Caucasian ratio and, therefore, our findings are not only important per se, but they constitute the basis for improved and more specific genetic counselling, as well as to support for preventive campaigns geared toward the Chilean population.
对来自智利的64个高危乳腺癌和/或卵巢癌家族样本进行筛查，以检测BRCA1基因（MIM编号113705）和BRCA2基因（MIM编号600185）编码序列及外显子-内含子边界的种系突变，采用构象敏感性凝胶电泳法进行检测，对发现的突变通过直接测序进行确认。发现7个家族（10.9%）携带BRCA1突变，3个家族（4.7%）有BRCA2突变。在BRCA1中检测到6种不同的致病突变，4种为先前报道过的（c.187_188delAG；c.300T→G，c.3450_3453delCAAG和IVS17-1G→A），2种为新突变（c.2605_2606delTT和c.4185_4188delCAAG）。在BRCA2中，发现3种不同的致病突变，2种为先前描述过的（c.6174delT和c.6503_6504delTT），1种为新突变（c.5667delT）。我们还鉴定出9种意义未明的变异（BRCA1中有5种，BRCA2中有4种）。这些发现表明智利人群中BRCA突变谱具有异质性。鉴于我们研究中获得的结果，对智利高危乳腺癌/卵巢癌患者进行分子遗传学检测时，有必要对整个BRCA1和BRCA2编码区进行筛查。据我们所知，这是在智利进行的首次BRCA基因突变的遗传学研究。智利人群具有众所周知的美洲印第安人与高加索人的混合比例，因此，我们的发现不仅本身具有重要意义，而且它们构成了改善和更具针对性的遗传咨询的基础，以及为面向智利人群的预防运动提供支持。
