P53 gene mutations and rearrangements in non-Hodgkin's lymphoma.

Abstract

Alterations of the p53 gene have been associated with the progression of certain human malignancies. To establish further the correlation between p53 gene alterations and progression of non-Hodgkin's lymphomas (NHLs), the authors analyzed both mutations and rearrangements of the p53 gene in a cohort of 84 NHLs. Eighty-four NHLs were analyzed for p53 gene alterations. Point mutations of exons 5-9 were studied by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), and DNA rearrangements were studied by Southern blot analysis. RESULTS. Point mutations and DNA rearrangements of the p53 gene were detected in 6 (7.2%) and 3 (3.6%) patients, respectively. All p53 gene abnormalities were found exclusively in B-cell NHLs. Taken together, patients with p53 gene alterations had poorer survival than other patients (P = 0.024). However, of the three patients with p53 gene rearrangements, the two who appeared to have one normal allele showed a relatively better response to chemotherapy and had longer survival (27 and 47 months). In contrast, the remaining patient who had rearranged bands much stronger than the germline, and thus appeared to have both alleles rearranged, was refractory to chemotherapy and had poorer survival (6 months). Patients with NHLs of intermediate and high grades who carried point mutations or rearrangements of p53 genes had worse outcomes than other patients. Patients with one abnormal p53 allele and one residual normal allele had a more favorable prognosis than those with two abnormal alleles.