p53 gene mutations and rearrangements in non-Hodgkin's lymphoma

BACKGROUND. Alterations of the p53 gene have been associated with the progr ession of certain human malignancies. To establish further the correlation between p53 gene alterations and progression of non-Hodgkin's lymphomas (NH Ls), the authors analyzed both mutations and rearrangements of the p53 gene in a cohort of 84 NHLs. METHODS. Eighty-four NHLs were analyzed for p53 gene alterations. Point mut a tions of exons 5-9 were studied by polymerase chain reaction-single stran d conformation polymorphism (PCR-SSCP), and DNA rearrangements were studied by Southern blot analysis. RESULTS, Point mutations and DNA rearrangements of the p53 gene were detect ed in 6 (7.2%) and 3 (3.6%) patients, respectively, All p53 gene abnormalit ies were found exclusively in B-cell NHLs. Taken together, patients with p5 3 gene alterations had poorer survival than other patients (P = 0.024). How ever, of the three patients with p53 gene rearrangements, the two who appea red to have one normal allele showed a relatively better response to chemot herapy and had longer survival (27 and 47 months). In contrast, the remaini ng patient who had rearranged bands much stronger than the germline, and th us appeared to have both alleles rearranged, was refractory to chemotherapy and had poorer survival (6 months). CONCLUSIONS, Patients with NHLs of intermediate and high grades who carried point mutations or rearrangements of p53 genes had worse outcomes than oth er patients. Patients with one abnormal p53 allele and one residual normal allele had a more favorable prognosis than those with two abnormal alleles. Cancer 1999;85: 718-24. (C) 1999 American Cancer Society.