Santarosa M, Dolcetti R, Magri M D, Crivellari D, Tibiletti M G, Gallo A, Tumolo S, Della Puppa L, Furlan D, Boiocchi M, Viel A
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano, Italy.
Int J Cancer. 1999 Sep 24;83(1):5-9. doi: 10.1002/(sici)1097-0215(19990924)83:1<5::aid-ijc2>3.0.co;2-u.
The heritable defects of BRCA1 and BRCA2 genes have been shown to predispose to breast and ovarian cancers. In a previous report, we analyzed 46 Italian families with breast and/or ovarian cancer for BRCA1 mutations. In the present study, those families and 11 others were screened for BRCA2 mutations; the newly enrolled families were also analyzed for the BRCA1 gene. The coding region and splice boundaries of BRCA2 and BRCA1 genes were assessed by the protein-truncation test and single-strand conformational polymorphism. A total of 20 different mutations were found in 21 families (37%). A total of 9 families (16%) showed mutations in the BRCA1 gene, including the one new mutation identified in this study (5382insC), and 12 families (21%) presented mutations in the BRCA2 gene. BRCA2-mutated families presented breast and ovarian cancers or breast cancers only, whereas most BRCA1-mutated families presented ovarian cancer alone or in association with breast cancer. All the BRCA2 mutations led to a truncated protein: 6 were frameshift mutations, 4 were non-sense mutations and 2 involved the intronic invariant region leading to splice variants. Therefore, in the Italian population, the cumulative proportion of BRCA1 and BRCA2 mutations was within the range observed in other studies (37%), with higher involvement of BRCA2 than of BRCA1. Many families in which no mutations were found presented a very high incidence of breast and/or ovarian cancer. Among the 36 BRCA1 and BRCA2 wild-type families, 24 presented at least 4 cancer cases, indicating the existence of other important predisposing genes.
BRCA1和BRCA2基因的遗传性缺陷已被证明易患乳腺癌和卵巢癌。在之前的一份报告中，我们分析了46个患有乳腺癌和/或卵巢癌的意大利家庭的BRCA1突变情况。在本研究中，对这些家庭以及另外11个家庭进行了BRCA2突变筛查；新纳入的家庭也进行了BRCA1基因分析。通过蛋白质截短试验和单链构象多态性评估BRCA2和BRCA1基因的编码区和剪接边界。在21个家庭（37%）中总共发现了20种不同的突变。共有9个家庭（16%）显示出BRCA1基因的突变，包括本研究中鉴定出的一个新突变（5382insC），12个家庭（21%）出现了BRCA2基因的突变。BRCA2突变的家庭患有乳腺癌和卵巢癌或仅患有乳腺癌，而大多数BRCA1突变的家庭仅患有卵巢癌或与乳腺癌并发。所有BRCA2突变均导致蛋白质截短：6个为移码突变，4个为无义突变，2个涉及内含子不变区导致剪接变异。因此，在意大利人群中，BRCA1和BRCA2突变的累积比例在其他研究观察到的范围内（37%），BRCA2的受累程度高于BRCA1。许多未发现突变的家庭中乳腺癌和/或卵巢癌的发病率非常高。在36个BRCA1和BRCA2野生型家庭中，24个家庭至少有4例癌症病例，表明存在其他重要的易感基因。
