Díez Gibert O, del Río E, Domènech M, Hernández E M, Sanz J, Brunet J, Alonso M C, Baiget M
Servicio de Genética, Hospital de Sant Pau, Barcelona.
Med Clin (Barc). 1999 Jan 23;112(2):51-4.
Germline mutations in the BRCA1 gene have been associated with familial breast/ovarian cancer. Furthermore, women diagnosed of early-onset breast cancer have a higher probability of being carriers of BRCA1 mutations. Our aim was to know prevalence of BRCA1 mutations in women with breast cancer diagnosed before 40 years.
We analyzed genomic DNA samples of 159 women with early-onset breast cancer. Ten fragments of BRCA1 gene covering the 36% of cases with mutations described in the literature were screened. Analysis involved polymerase chain reaction (PCR), single-strand conformation polymorphisms (SSCP) and direct sequencing.
Three germline BRCA1 mutations were identified, one of them not previously described. Two mutations were found in women with familial history of breast cancer. Five additional rare variants and polymorphisms were also detected.
The absence of recurrent mutations or mutations detected in other countries, except for the 185delAG mutation, present in Ashkenazim population, shows the influence of ethnic and geographic origin of population studied, and illustrates the difficulties of establishing DNA-based screening tests for hereditary breast cancer.
BRCA1基因的种系突变与家族性乳腺癌/卵巢癌相关。此外，被诊断为早发性乳腺癌的女性携带BRCA1突变的可能性更高。我们的目的是了解40岁之前被诊断为乳腺癌的女性中BRCA1突变的患病率。
我们分析了159例早发性乳腺癌女性的基因组DNA样本。筛选了BRCA1基因的十个片段，这些片段覆盖了文献中描述的36%的突变病例。分析包括聚合酶链反应（PCR）、单链构象多态性（SSCP）和直接测序。
鉴定出三个种系BRCA1突变，其中一个此前未被描述。在有乳腺癌家族史的女性中发现了两个突变。还检测到另外五个罕见变异和多态性。
除了在德系犹太人中存在的185delAG突变外，未发现其他国家中出现的复发性突变，这表明所研究人群的种族和地理起源的影响，并说明了建立基于DNA的遗传性乳腺癌筛查试验的困难。
