Prevalence of five previously reported and recurrent BRCA1 genetic rearrangement mutations in 20,000 patients from hereditary breast/ovarian cancer families
Prevalence of five previously reported and recurrent BRCA1 genetic rearrangement mutations in 20,000 patients from hereditary breast/ovarian cancer families
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DOI：
10.1002/gcc.20189
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发表时间：
2005-07-01
影响因子：
3.7
通讯作者：
Scholl, T
中科院分区：
文献类型：
--
作者：
Hendrickson, BC;Judkins, T;Scholl, T
BRCA 1基因中的许多重排突变已被确定。越来越清楚的是，这些突变中的一些是普遍的，因此它们的检测是必要的，以便福特临床基因检测具有高灵敏度。发表的关于特定重排的信息通常仅限于单个患者、少数患者或特定种族的患者。这项工作的目的包括表征在一个大型北美患者人群中五种特定重排突变的患病率。突变特异性多重PCR检测用于确定5个BRCA 1重排突变的患病率，这些突变以前曾报告发生在无关患者中。这些重排的突变状态来自20，712名遗传性乳腺癌和/或卵巢癌高危患者，他们提交了临床基因检测样本。从2,634名突变携带者中获得的结果显示，在53名患者中发现了外显子13的6 kb重复（2.01%）; 7例患者中检测到26-kb的缺失，包括外显子1420 5例患者（0.19%）检测到外显子22的510-bp缺失; 1例患者（0.04%）检测到外显子13的3.4-kb缺失。未发现以前报道的外显子8-9的7.1kb缺失，外显子13的高频率重复使其成为这些患者中第四大常见突变。这些结果提供了这些突变在北美接受基因检测的遗传性乳腺癌/卵巢癌患者中的患病率的准确情况。(c)2005 Wiley-Liss，Inc.
Many rearrangement mutations in the BRCA1 gene have been identified. It is becoming clear that some of these mutations are prevalent, and therefore their detection is necessary in order ford clinical genetic tests to have high sensitivity. Published information on particular rearrangements is frequently limited to a single patient, small groups of patients, or patients of a particular ethnicity. The objectives of this work included characterizing the prevalence of five specific rearrangement mutations in a large North American patient population. A mutation-specific multiplex PCR assay was used for determining the prevalence of five BRCA1 rearrangement mutations that previously had been reported to occur in unrelated patients. The mutation status of these rearrangements, which came from 20,712 patients at high risk for hereditary breast and/or ovarian cancers who had submitted specimens for clinical genetic testing, is presented. The results, obtained from 2,634 mutation carriers, showed a 6-kb duplication of exon 13, identified in 53 patients (2.01%); a 26-kb deletion encompassing exons 1420, detected in seven patients (0.27%); a 510-bp deletion of exon 22, detected in 5 patients (0.19%); and a 3.4-kb deletion of exon 13, detected in one patient (0.04%). A previously reported 7.1-kb deletion of exons 8-9 was not found. The high frequency of the exon 13 duplication makes it the fourth most prevalent mutation in these patients. These results provide an accurate picture of the prevalence of these mutations in hereditary breast/ovarian cancer patients undergoing genetic testing in North America. (c) 2005 Wiley-Liss, Inc.