P53 mutation in advanced stage of primary myelodysplastic syndrome

Polymerase chain reaction and single strand conformation polymorphism (PCR- SSCP) analysis of the p53 tumor suppressor gene (from exon 2 to 9) was perf ormed on samples from 47 adult patients with primary myelodysplastic syndro me (MDS). Point mutation was found in 5 (11%) patients: exon 7 in 3, exon 4 in 1 and intron 5 in 1. The frequency of p53 mutation was significantly hi gher at advanced stages (p = 0.048) and higher in patients with abnormal ka ryotypes (p = 0.023). Although all of the p53 mutations were detected at ad vanced stages, four of them were detected at initial diagnosis with very sh ort survival. Sequential SSCP analysis in 20 transformed MDS patients revea led only one new p53 mutation during progression from early MDS phases. The results suggest that p53 mutation might occur as an early genetic event an d is probably associated with rapid progression and poor survival in some M DS patients.