NEUROFIBROMATOSIS-1 GENE (NF1) MUTATION IS A RARE GENETIC EVENT IN MYELODYSPLASTIC SYNDROME REGARDLESS OF THE DISEASE PROGRESSION

Neurofibromatosis 1 gene (NF1) is a tumor suppressor gene and the prod uct of which down-regulates Nras protein by its GTPase activating prot ein-related domain (NF1-GRD). Although the incidence of NF1 mutation w as reported to be rare in the chronic phase of myelodysplastic syndrom e (MDS), there have been no previous reports on its configuration in p atients showing the disease progression. We examined NF1 in 50 patient s with MDS including 9 who had progressed to more advanced stages and 16 to acute leukemia. Six patients had an Nras mutation. We carried ou t allele specific restriction analysis (ASRA) to detect a mutation at the first nucleotide A of codon 1423 (AAG), a mutational hot spot. We also employed a polymerase chain reaction mediated single strand confo rmation polymorphism (PCR-SSCP) method to confirm the result of ASRA a nd to detect a point mutation in other sequences of FLR exon. In conse quence, ASRA disclosed wild type configuration and PCR-SSCP showed no aberrant band in any sample examined whether the samples harboured an Nras mutation or not. We conclude that NF1 mutation does not play a cr ucial role in the development and the progression of MDS.