Characterization of common BRCA1 and BRCA2 variants
Characterization of common BRCA1 and BRCA2 variants
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DOI：
10.1089/10906570260199375
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发表时间：
2002-06-01
期刊：
影响因子：
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通讯作者：
Neuhausen, SL
中科院分区：
文献类型：
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作者：
Deffenbaugh, AM;Frank, TS;Neuhausen, SL
在BRCA1和BRCA2中发现的许多错义变异，这两个基因负责大多数遗传性乳腺癌和卵巢癌，临床意义尚不清楚。表征这些变体的显著性对于在其中鉴定它们的患者的医学管理是重要的。这项研究的目的是描述8种最常见的BRCA1和BRCA2错义突变，这些突变发生在乳腺癌和卵巢癌遗传风险检测的患者中。考虑了对照人群中每种变体的患病率、家族内变体与癌症的共分离、变体在基因内的位置、氨基酸取代的性质和物种间野生型氨基酸的保守性。在对照人群中，BRCA1变异体M1652 I、R1347 G和S1512 I的频率分别为4.08%、2.04%和2.04%，BRCA2变异体A2951 T、V2728 I和D1420 Y的频率分别为1.02%、0.68%和0.34%。尽管在这组对照中未观察到BRCA2变体T598A和R2034C，但其他临床和已发表的观察结果表明这些变体无害。基于流行病学和生物学标准，我们因此得出结论，BRCA1错义突变R1347 G，S1512 I和M1652 I，以及BRCA2错义突变T598 A，D1420 Y，R2034 C，V2728 I和A2951 T不是有害突变。
Many missense variants identified in BRCA1 and BRCA2, two genes responsible for the majority of hereditary breast and ovarian cancer, are of unclear clinical significance. Characterizing the significance of such variants is important for medical management of patients in whom they are identified. The aim of this study was to characterize eight of the most common reported missense mutations in BRCA1 and BRCA2 occurring in patients tested for hereditary risk of breast and ovarian cancers. The prevalence of each variant in a control population, co-segregation of the variant with cancer within families, location of the variant within the gene, the nature of the amino acid substitution and conservation of the wild-type amino acid among species were considered. In a control population, the BRCA1 variants M1652I, R1347G, and S1512I, were each observed at a frequency of 4.08%, 2.04%, and 2.04%, respectively, and the BRCA2 variants A2951T, V2728I, and D1420Y, were seen at 1.02%, 0.68%, and 0.34%, respectively. Although the BRCA2 variants T598A and R2034C were not seen in this group of controls, other clinical and published observations indicate that these variants are not deleterious. Based on epidemiological and biological criteria, we therefore conclude that the BRCA1 missense mutations R1347G, S1512I and M1652I, and the BRCA2 missense mutations T598A, D1420Y, R2034C, V2728I, and A2951T, are not deleterious mutations.