title: UMD-MLH1/MSH2/MSH6 databases: description and analysis of genetic variations in French Lynch syndrome families.
abstract: Lynch syndrome is an autosomal dominant disease caused by germ line heterozygous mutations mainly involving the MSH2, MLH1 and MSH6 genes that belong to the DNA MisMatch Repair (MMR) genes family. The French network counting the 16 licensed laboratories involved in Lynch syndrome genetic testing developed three locus-specific databases with the UMD software (www.umd.be/MLH1/, www.umd.be/MSH2/ and www.umd.be/MSH6/) that presently contain a total of 7047 sequence variations including 707 distinct variations of a priori unknown functional significance (VUS) that were identified through complete mutation screening or targeted predictive testing. Mutation carriers are at high risk for developing early-onset colorectal and endometrial adenocarcinomas. Consensus clinical guidelines have been proposed, allowing the efficient detection of curable lesions. The major challenge of genetic testing is to reliably classify the genomic variations in those patients who seek genetic counseling. Combining the interactive tools of the software, the relevant published data and mainly original information produced by the French MisMatch Repair network, the UMD-MLH1/MSH2/MSH6 databases provide interpretation data for the 707 VUS that were classified according to the IARC 5-Class system. These public databases are regularly updated to improve the classification of all registered VUS, exploring their role in cancer pre-disposition based on structural and functional approaches.
authors.affiliation: UMR_S910, INSERM, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandval
authors.forename: Aurélie J
authors.initials: AJ
authors.lastname: Fabre
authors.forename: Pascaline
authors.initials: P
authors.lastname: Gaildrat
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baert-Desurmont
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Anthony
authors.initials: A
authors.lastname: Ferrari
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D005190:Family; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D012984:Software
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein