Mutational analysis of p53 in 16 cases of acute lymphoblastic leukemia and Burkitt's lymphoma.

BACKGROUND AND

OBJECTIVE

Improvements in therapy for patients with B-cell acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) depend on the identification of subsets of patients who require more intensive therapy. Abnormalities of the p53 gene are the most common molecular lesions in human cancer, and may be of prognostic significance in hematologic malignancies. In this study, we examined the p53 gene status in a group of patients with ALL/BL to determine whether some types of mutants were more frequent in this selected group of patients.

METHODS

We selected a group of 16 patients with acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) in order to investigate the presence of p53 mutations. DNA obtained from affected organs (bone marrow, lymph node and a renal mass) was used for the molecular studies. Single-strand conformation polymorphism (SSCP) analysis of exons 5 to 9 of the gene was used to detect p53 mutants. After detecting an abnormal migration pattern on the SSCP, mutations were determined by direct sequencing.

RESULTS

Point mutations were found in eight patients; a misense mutation in seven cases and a non-sense mutation in one case. The normal allele was also identified in 7 mutated samples. The same mutation 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 after a BMT. No such alteration was present in the bone marrow analyzed at the same time.

INTERPRETATION AND

CONCLUSIONS

Our findings suggest that p53 mutations are quite frequent in recognized clinical groups. The criteria chosen in this study allowed us to identify a high percentage of the samples with mutation. Different malignant phenotypes could be determined by functional heterogeneity of p53 mutants.