A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO
A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO
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DOI：
10.1136/jmg.2003.017996
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发表时间：
2004-06-01
影响因子：
4
通讯作者：
Lalloo, F
中科院分区：
文献类型：
--
作者：
Evans, DGR;Eccles, DM;Lalloo, F
目的：为了开发一个简单的评分系统的可能性，确定一个BRCA 1或BRCA 2 mutation.Methods：DNA样本从受影响的受试者从422个非犹太人的乳腺癌和/或卵巢癌的历史进行了筛选BRCA 1突变和一个子集的318个BRCA 2筛选全基因筛选技术。使用筛选结果和突变阴性和阳性激酶家族史的组合，设计了一个简单的评分系统（曼彻斯特评分系统）来预测致病性突变，特别是在10%的可能性水平上进行区分。随后使用192个样本的第二个单独数据集来测试模型的预测值。这是进一步验证了第三组258个样本，并与现有的models.Results：评分系统包括一个截止在10个点为每个基因进行比较。这相当于BRCA 1和BRCA 2中致病性突变的概率>10%。曼彻斯特评分系统的灵敏度和特异性之间的最佳权衡在10%的预测突变的存在所示的最高的C-统计量，是远远上级BRCAPRO.Conclusion：该评分系统是有用的，特别是在识别突变BRCA 2。在计算是否筛查BRCA 1突变时，该算法可能需要修改以包括病理数据。对于临床医生来说，这比使用计算机模型要耗时少得多，如果在临床实践中常规实施，将有助于选择最适合用于诊断测试的DNA采样的家庭。
Purpose: To develop a simple scoring system for the likelihood of identifying a BRCA1 or BRCA2 mutation.Methods: DNA samples from affected subjects from 422 non-Jewish families with a history of breast and/ or ovarian cancer were screened for BRCA1 mutations and a subset of 318 was screened for BRCA2 by whole gene screening techniques. Using a combination of results from screening and the family history of mutation negative and positive kindreds, a simple scoring system ( Manchester scoring system) was devised to predict pathogenic mutations and particularly to discriminate at the 10% likelihood level. A second separate dataset of 192 samples was subsequently used to test the model's predictive value. This was further validated on a third set of 258 samples and compared against existing models.Results: The scoring system includes a cut-off at 10 points for each gene. This equates to >10% probability of a pathogenic mutation in BRCA1 and BRCA2 individually. The Manchester scoring system had the best trade-off between sensitivity and specificity at 10% prediction for the presence of mutations as shown by its highest C-statistic and was far superior to BRCAPRO.Conclusion: The scoring system is useful in identifying mutations particularly in BRCA2. The algorithm may need modifying to include pathological data when calculating whether to screen for BRCA1 mutations. It is considerably less time-consuming for clinicians than using computer models and if implemented routinely in clinical practice will aid in selecting families most suitable for DNA sampling for diagnostic testing.