title: Detection of exon deletions and duplications of the mismatch repair genes in hereditary nonpolyposis colorectal cancer families using multiplex polymerase chain reaction of short fluorescent fragments.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, EPI 9906, Faculté de Médecine et de Pharmacie, Rouen, France.
authors.forename: F
authors.initials: F
authors.lastname: Charbonnier
authors.forename: G
authors.initials: G
authors.lastname: Raux
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Drouot
authors.forename: F
authors.initials: F
authors.lastname: Cordier
authors.forename: J M
authors.initials: JM
authors.lastname: Limacher
authors.forename: J C
authors.initials: JC
authors.lastname: Saurin
authors.forename: A
authors.initials: A
authors.lastname: Puisieux
authors.forename: S
authors.initials: S
authors.lastname: Olschwang
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D005091:Exons; D005192:Family Health; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D007438:Introns; D008957:Models, Genetic; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein