Establishing a control population to screen for the occurrence of nineteen unclassified variants in the BRCA1 gene by denaturing high-performance liquid chromatography
Establishing a control population to screen for the occurrence of nineteen unclassified variants in the BRCA1 gene by denaturing high-performance liquid chromatography
复制标题
DOI：
10.1016/s1570-0232(02)00696-7
复制
发表时间：
2002-12-25
影响因子：
3
通讯作者：
Jonat, W
中科院分区：
文献类型：
--
作者：
Arnold, N;Peper, H;Jonat, W
在乳腺癌和卵巢癌患者的临床筛查过程中检测到许多BRCA1和BRCA2的错义突变。由于缺乏功能性蛋白质测定来确定这些突变的功能性后果，患者经常因未分类的变体（UV）而导致的不确定结果而感到沮丧。为了确定报告的UV是否也存在于对照组中，因此更可能是一种罕见的多态性而不是有害的突变，我们收集了一个对照人群，包括95名女性和25名男性，年龄超过60岁（平均73岁），没有BRCA相关癌症的家族史。对照组的年龄超过遗传背景的乳腺癌和卵巢癌的发病中位数。采用DHPLC技术分析这些对照品中BRCA 1中是否存在19种已知UV。19种变体中仅检测到4种（R496 H、R866 C、S1040 N和M16521），可以认为是多态性。然而，关于其他15个变体的功能相关性，无法得出确切的结论。(C)2002 Elsevier Science B.V.保留所有权利。
Numerous missense mutations in BRCA1 and BRCA2 are detected during clinical screening of breast and ovarian cancer patients. Because of the lack of a functional protein assay to determine the functional consequence of these mutations, patients are often frustrated by inconclusive results due to unclassified variants (UV). To determine whether a reported UV is also present in a control collective and therefore more likely be a rare polymorphism than a deleterious mutation, we collected a control population consisting of 95 females and 25 males aged over 60 years (mean 73 years) without a family history of BRCA associated cancers. The age of the control group is beyond the median onset of breast and ovarian cancer with a hereditary background. These controls were analysed for the presence of 19 known UVs in BRCA1 with the DHPLC technique. Only four of the 19 variants (R496H, R866C, S1040N and M16521) were detected and can be considered polymorphims. However, no firm conclusion can be drawn about the functional relevance of the other 15 variants. (C) 2002 Elsevier Science B.V. All rights reserved.