Baert-Desurmont Stephanie, Buisine Marie-Pierre, Bessenay Emilie, Frerot Stephanie, Lovecchio Tonio, Martin Cosette, Olschwang Sylviane, Wang Qing, Frebourg Thierry
Inserm U614, Faculty of Medicine, Rouen, France and Department of Genetics, Rouen University Hospital, Rouen, France.
Eur J Hum Genet. 2007 Mar;15(3):383-6. doi: 10.1038/sj.ejhg.5201765. Epub 2007 Jan 17.
Numerous reports have highlighted the contribution of MSH2 and MLH1 genomic deletions to hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch's syndrome, but genomic duplications of these genes have been rarely reported. Using quantitative multiplex PCR of short fluorescent fragments (QMPSF), 962 and 611 index cases were, respectively, screened for MSH2 and MLH1 genomic rearrangements. This allowed us to detect, in 11 families, seven MSH2 duplications affecting exons 1-2-3, exons 4-5-6, exon 7, exons 7-8, exons 9-10, exon 11, and exon 15, and three MLH1 duplications affecting exons 2-3, exon 4 and exons 6-7-8. All duplications were confirmed by an independent method. The contribution of genomic duplications of MSH2 and MLH1 to HNPCC can therefore be estimated approximately to 1% of the HNPCC cases. Although this frequency is much lower than that of genomic deletions, the presence of MSH2 or MLH1 genomic duplications should be considered in HNPCC families without detectable point mutations.
众多报告强调了MSH2和MLH1基因缺失对遗传性非息肉病性结直肠癌（HNPCC）或林奇综合征的影响，但这些基因的基因组重复鲜有报道。我们采用短荧光片段定量多重PCR（QMPSF）技术，分别对962例和611例索引病例进行了MSH2和MLH1基因重排的筛查。通过该技术，我们在11个家族中检测到7例MSH2重复，分别影响外显子1 - 2 - 3、外显子4 - 5 - 6、外显子7、外显子7 - 8、外显子9 - 10、外显子11和外显子15；以及3例MLH1重复，分别影响外显子2 - 3、外显子4和外显子6 - 7 - 8。所有重复均通过独立方法得到确认。因此，MSH2和MLH1基因重复对HNPCC的影响约占HNPCC病例的1%。尽管这一频率远低于基因缺失的频率，但对于未检测到点突变的HNPCC家族，应考虑存在MSH2或MLH1基因重复的可能性。
