MUTATIONAL ANALYSIS OF P53 IN 16 CASES OF ACUTE LYMPHOBLASTIC-LEUKEMIA AND BURKITTS-LYMPHOMA

Background and Objective. Improvements in therapy for patients with B- cell acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) de pend on the identification of subsets of patients who require more int ensive therapy. Abnormalities of the p53 gene are the most common mole cular lesions in human cancer, and may be of prognostic significance i n hematologic malignancies. In this study, we examined the p53 gene st atus in a group of patients with ALL/BL to determine whether some type s of mutants were more frequent in this selected group of patients. Me thods. We selected a group of 16 patients with acute lymphoblastic leu kemia (ALL) and Burkitt's lymphoma (BL) in order to investigate the pr esence of p53 mutations. DNA obtained from affected organs (bone marro w, lymph node and a renal mass) was used for the molecular studies. Si ngle-strand conformation polymorphism (SSCP) analysis of exons 5 to 9 of the gene was used to detect p53 mutants. After detecting an abnorma l migration pattern on the SSCP, mutations were determined by direct s equencing. Results. Point mutations were found in eight patients; a mi sense mutation in seven cases and a non-sense mutation in one case. Th e normal allele was also identified in 7 mutated samples. The same mut ation at codon 282 was identified in three different patients, in whom an identical conformer was detected after SSCP analysis. Mutation at codon 282 was present in an extramedular relapse (renal) appearing aft er a BMT. No such alteration was present in the bone marrow analyzed a t the same time. Interpretation and Conclusions. Our findings suggest that p53 mutations are quite frequent in recognized clinical groups. T he criteria chosen in this study allowed us to identify a high percent age of the samples with mutation. Different malignant phenotypes could be determined by functional heterogeneity of p53 mutants.