Loss of heterozygosity analysis at the BRCA loci in tumor samples from patients with familial breast cancer
Loss of heterozygosity analysis at the BRCA loci in tumor samples from patients with familial breast cancer
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DOI：
10.1002/ijc.10337
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发表时间：
2002-05-10
影响因子：
6.4
通讯作者：
Benítez, J
中科院分区：
文献类型：
--
作者：
Osorio, A;de la Hoya, M;Benítez, J
BRCA 1和BRCA 2基因是导致家族性乳腺癌的高比例的原因;这些基因中的生殖系突变赋予患乳腺癌的约70%的终生风险。大多数描述的有害突变是源自截短蛋白质的小缺失或插入;然而，在许多情况下，它们是意义未知的氨基酸变化。在这些情况下，有一些测试可以分析这些变体的含义，但大多数仍然未分类。BRCA基因是肿瘤抑制基因，人们认为野生型等位基因的完全缺失是这些基因中携带生殖系有害突变的患者的肿瘤失活的常见机制;如果这是真的，那么肿瘤样本中的杂合性缺失（洛）分析可以帮助区分罕见变异是有害突变还是常见多态性。在本研究中，我们对47例乳腺癌患者的BRCA基因座进行了洛缺失分析，这些患者均属于高危乳腺癌家族，并且是这些基因任何类型变异的携带者。我们的研究结果表明，（i）野生型等位基因的丢失是任何基因携带有害突变的患者的肿瘤中最常见的失活机制，（ii）当我们分析与BRCA突变无关的家族性肿瘤时，这种丢失并不常见，（iii）洛可用于阐明BRCA基因中未知意义的变异。(C)2002 Wiley-Liss，Inc.
The BRCA1 and BRCA2 genes are responsible for a high proportion of familial breast cancer; germline mutations in these genes confer a lifetime risk of about 70% for developing breast cancer. Most of the described deleterious mutations are small deletions or insertions that originate a truncated protein; however, in many cases, they are amino acid changes whose significance is unknown. In these cases, there are some tests that can analyze the meaning of these variants, but most remain unclassified. The BRCA genes are tumor supressors and it is beleived that complete loss of the wild-type allele is a common mechanism of inactivation in tumors from patients carrying a germline deleterious mutation in these genes; if this is true, loss of heterozygosity (LOH) analysis in the tumor sample could help to distinguish if a rare variant is either a deleterious mutation or a common polymorphism. In the present study, we performed LOH analysis at the BRCA loci in 47 tumors from patients who belonged to high-risk breast cancer families and were carriers of any type of alteration in these genes. Our results suggest that (i) loss of the wild-type allele is the most common mechanism of inactivation in tumors from patients who carry a deleterious mutation in any of the genes, (ii) this loss is not common when we analyze familial tumors not associated with mutations in BRCA and (iii) LOH can be used to clarify variants of unknown significance in the BRCA genes. (C) 2002 Wiley-Liss, Inc.