title: Partial duplications of the MSH2 and MLH1 genes in hereditary nonpolyposis colorectal cancer.
abstract: 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.
authors.affiliation: Inserm U614, Faculty of Medicine, Rouen, France and Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Baert-Desurmont
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Emilie
authors.initials: E
authors.lastname: Bessenay
authors.forename: Stephanie
authors.initials: S
authors.lastname: Frerot
authors.forename: Tonio
authors.initials: T
authors.lastname: Lovecchio
authors.forename: Cosette
authors.initials: C
authors.lastname: Martin
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein