DELETIONS AND REARRANGEMENTS OF CYCLIN-DEPENDENT KINASE-4 INHIBITOR GENE P16 ARE ASSOCIATED WITH POOR-PROGNOSIS IN B-CELL NON-HODGKINS-LYMPHOMAS

In the present study we examined by Southern blot analysis the presenc e of deletions and rearrangements of the p16 tumor-suppressor gene in B cell non-Hodgkin's lymphomas (NHLs) in order to determine whether or not these changes can be related to a particular histological subtype and the different clinico-biological and prognostic characteristics o f the disease. 103 untreated patients were enrolled in the study. Seve n cases displayed alterations in the p16 gene: four cases with homozyg ous deletions and three with gene rearrangement. The presence of these abnormalities did not correlate with any specific histological subtyp e: three cases were small lymphocytic lymphomas (two of them reclassif ied as mantle cell lymphoma on the basis of the REAL classification), two diffuse large cell lymphomas and two small non-cleaved cell lympho mas (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, and this was confirmed in the survival analysis, since the presence of pie gene abnormalities was as sociated with a shorter survival (10 vs 81 months, P = 0.0006). In the multivariate analysis, pie abnormalities were selected as an independ ent prognostic factor together with the LDH and beta(2)-microglobulin. These findings support a role for the p16 gene in the pathogenesis of B cell NHLs and suggest an association of pie abnormalities with aggr essive forms of the disease that could be useful to predict the progno sis of patients.