title: [HNPCC syndrome, microsatellite instability and NF1 gene alteration].
abstract: Hereditary predisposition to non polyposis colorectal cancer is caused by a heterozygous germline mutation in a DNA mismatch repair gene (essentially hMLH1 or hMSH2). Cancer progression in predisposed individuals results from the occurrence of a somatic alteration of the normal copy of the gene. Recently, we identified children with a constitutional deficiency of mismatch repair activity, due to a homozygous germline mutation of the hMLH1 gene. These children exhibited clinical features of de novo neurofibromatosis type 1 and early onset of hematopoietic cancers. This observation demonstrates that mismatch repair deficiency is compatible with human development. However, the subsequent genetic instability leads to a high cancer susceptibility. In this context, the NF1 gene appears to be a preferential mutational target. Implications of this observation are discussed.
authors.affiliation: Unité d'oncologie moléculaire, unité Inserm U. 453, centre Léon-Bérard, 28, rue Laennec, 69000 Lyon Cedex 08.
authors.forename: A
authors.initials: A
authors.lastname: Puisieux
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000235:genetics; D009687:Nuclear Proteins; 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; D000251:Adenosine Triphosphatases; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein