Charbonnier F, Raux G, Wang Q, Drouot N, Cordier F, Limacher J M, Saurin J C, Puisieux A, Olschwang S, Frebourg T
Institut National de la Santé et de la Recherche Médicale, EPI 9906, Faculté de Médecine et de Pharmacie, Rouen, France.
Cancer Res. 2000 Jun 1;60(11):2760-3.
Large genomic deletions within the mismatch repair MLH1 and MSH2 genes have been identified in families with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, and their detection represents a technical problem. To facilitate their detection, we developed a simple semiquantitative procedure based on the multiplex PCR of short fluorescent fragments. This method allowed us to confirm in HNPCC families three known deletions of MLH1 or MSH2 and to detect in 19 HNPCC families, in which analysis of mismatch repair genes using classical methods had revealed no alteration, a deletion of exon 5 and a duplication of MSH2 involving exons 9 and 10. The presence of such duplications, the frequency of which is probably underestimated, must be considered in HNPCC families in which conventional screening methods have failed to detect mutations.
在遗传性非息肉病性结直肠癌（HNPCC）综合征家族中，已鉴定出错配修复基因MLH1和MSH2内的大片段基因组缺失，其检测是一个技术难题。为便于检测，我们基于短荧光片段的多重PCR开发了一种简单的半定量方法。该方法使我们能够在HNPCC家族中确认MLH1或MSH2的三个已知缺失，并在19个HNPCC家族中检测到，其中使用经典方法对错配修复基因的分析未发现改变，即外显子5缺失以及涉及外显子9和10的MSH2重复。在传统筛查方法未能检测到突变的HNPCC家族中，必须考虑此类重复的存在，其频率可能被低估。
