Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type

摘要: DNA mismatch repair (MMR) is the process by which incorrectly paired nucleotides are recognized and repaired. A germline mutation in one of genes involved may be responsible for a dominantly inherited cancer syndrome, hereditary nonpolyposis colon cancer. Cancer progression predisposed individuals results from somatic inactivation normal copy MMR gene, leading to mutator phenotype affecting preferentially repeat sequences (microsatellite instability, MSI). Recently, we identified children with constitutional deficiency activity attributable hMLH1 gene. These exhibited genetic instability associated clinical features de novo neurofibromatosis type 1 (NF1) early onset extracolonic Based on these observations, hypothesized that NF1 gene was frequent possibly event MMR-deficient cells. To test this hypothesis, screened mutations Genetic alterations were five out ten tumor cell lines MSI, whereas MMR-proficient expressed wild-type Somatic also detected two primary tumors exhibiting an MSI phenotype. Finally, 35-bp deletion murine Nf1 coding region mlh1–/– mouse embryonic fibroblasts. observations demonstrate mutational target suggest its important step malignant