Deletions and rearrangements of cyclin-dependent kinase 4 inhibitor gene p16 are associated with poor prognosis in B cell non-Hodgkin’s lymphomas

Abstract

[EN]In the present study we examined by southern blot analysis the presence of deletions and rearrangements of the p16 tumour-supressor gene in B-cell Non-HodgkinÕs Lymphomas (NHLs) in order to determine wether or not these changes can be related with a particular histological subtype and the different clinico-biological and prognostic characteristics of the disease. 103 untreated patients were enrolled in the study. Seven cases displayed alterations in the p16 gene: four cases with homozygous deletions and three with gene rearrangement. The presence of these abnormalities did not correlate with any specific histological subtype: three cases were small lymphocytic lymphomas (two of them reclassified as mantle cell lymphoma on the basis of the REAL classification), two diffuse large cell lymphomas and two small non-cleaved cell lymphomas (one of them considered to be a Burkitt-like lymphoma according to the REAL). These seven cases showed a trend towards worse prognostic indicators than the remaining patients, an this was confirmed in the survival analysis, since the presence of p16 gene abnormalities was associated with a shorter survival (10 vs 81 months, p=0.0006). In the multivariate analysis, p16 abnormalities were selected as an independent prognostic factor together with the LDH and b2microglobulin. These findings support a role for the p16 gene in the pathogenesis of B-cell NHLs and suggest an association of p16 abnormalities with aggresive forms of the disease that could be useful to predict the prognosis of patients.