Tavtigian S V, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, Merajver S, Thorlacius S, Offit K, Stoppa-Lyonnet D, Belanger C, Bell R, Berry S, Bogden R, Chen Q, Davis T, Dumont M, Frye C, Hattier T, Jammulapati S, Janecki T, Jiang P, Kehrer R, Leblanc J F, Mitchell J T, McArthur-Morrison J, Nguyen K, Peng Y, Samson C, Schroeder M, Snyder S C, Steele L, Stringfellow M, Stroup C, Swedlund B, Swense J, Teng D, Thomas A, Tran T, Tranchant M, Weaver-Feldhaus J, Wong A K, Shizuya H, Eyfjord J E, Cannon-Albright L, Tranchant M, Labrie F, Skolnick M H, Weber B, Kamb A, Goldgar D E
Myriad Genetics Inc., Salt Lake City, Utah, USA.
Nat Genet. 1996 Mar;12(3):333-7. doi: 10.1038/ng0396-333.
Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.
在发达国家，乳腺癌是女性中最常见的恶性肿瘤。由于家族病史仍然是乳腺癌风险最强的单一预测因素，因此注意力集中在高外显率、显性遗传基因在癌症高发家族中的作用上（1）。通过对一组高危家族的分析，BRCA1被定位到17号染色体上（2），四年后通过定位克隆策略被鉴定出来（3）。大约在同一时间，BRCA2被定位到13号染色体长臂（4）。仅仅15个月后，伍斯特等人（5）报告了部分BRCA2序列以及6个预测会导致BRCA2蛋白截短的突变。虽然这些发现提供了有力证据，证明所鉴定的基因就是BRCA2，但仅分离并筛选了三分之二的编码序列和27个外显子中的8个；因此，关于BRCA2的性质以及13号染色体长臂连锁家族中的突变频率，仍有几个问题未得到解答。我们现已确定了BRCA2的完整编码序列和外显子结构（GenBank登录号#U43746），并研究了其表达模式。在此，我们提供了一组PCR引物的序列，足以使用基因组DNA筛选BRCA2的整个编码序列。我们还报告了对基于连锁分析和/或存在一例或多例男性乳腺癌而选择的家族中BRCA2的突变分析。连同先前描述的特定突变，我们的数据为BRCA2突变谱提供了初步见解。
