Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach.
Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach.
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DOI：
10.1038/sj.bjc.6600565
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发表时间：
2002-10-07
影响因子：
8.8
通讯作者：
Menko, FH
中科院分区：
文献类型：
--
作者：
Gille, JJP;Hogervorst, FBL;Pals, G;Wijnen, JT;van Schooten, RJ;Dommering, CJ;Meijer, GA;Craanen, ME;Nederlof, PM;de Jong, D;McElgunn, CJ;Schouten, JP;Menko, FH
遗传性非息肉病性结直肠癌是一种常染色体显性疾病，由于DNA错配修复基因的种系突变，特别是MLH 1，MSH 2和MSH 6。在这里，我们描述了一种新的技术用于检测MLH 1和MSH 2的基因组缺失的应用。该方法称为多重连接依赖性探针扩增，是一种定量多重PCR方法，用于测定每个MLH 1和MSH 2外显子的相对拷贝数。在126个根据临床标准选择的结直肠癌家族中进行基因突变筛查，此外，对于一个家族子集，肿瘤中存在微卫星不稳定性（MSI高）。在37个（29.4%）这些激酶中检测到38个种系突变，其中31个具有预测的致病作用。在MSI高肿瘤家族中，65.7%的人存在生殖系基因缺陷。基因组缺失占致病突变的54.8%。在两个家系中检测到MLH 1基因的完全缺失。多重连接依赖性探针扩增方法是一种快速检测MLH 1和MSH 2基因组缺失的方法。此外，它还揭示了使用传统诊断技术可能无法检测到的变化。多重连接依赖探针扩增技术可能被认为是遗传性非息肉病性结直肠癌分子诊断的早期步骤。英国癌症杂志（2002）87，892-897。www.bjcancer.com © 2002英国癌症研究中心
Hereditary non-polyposis colorectal cancer is an autosomal dominant condition due to germline mutations in DNA-mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Here we describe the application of a novel technique for the detection of genomic deletions in MLH1 and MSH2. This method, called multiplex ligation-dependent probe amplification, is a quantitative multiplex PCR approach to determine the relative copy number of each MLH1 and MSH2 exon. Mutation screening of genes was performed in 126 colorectal cancer families selected on the basis of clinical criteria and in addition, for a subset of families, the presence of microsatellite instability (MSI-high) in tumours. Thirty-eight germline mutations were detected in 37 (29.4%) of these kindreds, 31 of which have a predicted pathogenic effect. Among families with MSI-high tumours 65.7% harboured germline gene defects. Genomic deletions accounted for 54.8% of the pathogenic mutations. A complete deletion of the MLH1 gene was detected in two families. The multiplex ligation-dependent probe amplification approach is a rapid method for the detection of genomic deletions in MLH1 and MSH2. In addition, it reveals alterations that might escape detection using conventional diagnostic techniques. Multiplex ligation-dependent probe amplification might be considered as an early step in the molecular diagnosis of hereditary non-polyposis colorectal cancer. British Journal of Cancer (2002) 87, 892–897. doi:10.1038/sj.bjc.6600565 www.bjcancer.com © 2002 Cancer Research UK
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影响因子：
9.8
作者：
Berends, MJW;Wu, Y;Kleibeuker, JH
通讯作者：
Kleibeuker, JH
影响因子：
82.9
作者：
NYSTROMLAHTI, M;KRISTO, P;PELTOMAKI, P
通讯作者：
PELTOMAKI, P
DOI：
10.7326/0003-4819-135-8_part_1-200110160-00007
发表时间：
2001-10-16
影响因子：
39.2
作者：
Raedle, J;Trojan, J;Zeuzem, S
通讯作者：
Zeuzem, S
影响因子：
29.4
作者：
Trojan, J;Zeuzem, S;Marra, G
通讯作者：
Marra, G
影响因子：
9.8
作者：
Wijnen, J;Khan, PM;Fodde, R
通讯作者：
Fodde, R