Deletions and rearrangements of cyclin-dependent kinase 4 inhibitor gene p16 are associated with poor prognosis in B cell non-Hodgkin's lymphomas.
In the present study we examined by Southern blot analysis the presence 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 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, and 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 beta2-microglobulin. These findings support a role for the p16 gene in the pathogenesis of B cell NHLs and suggest an association of p16 abnormalities with aggressive forms of the disease that could be useful to predict the prognosis of patients.
García-Sanz
R
R
Department of Hematology, University Hospital of Salamanca, Paseo de San Vicente, Spain.
González
M
M
Vargas
M
M
Chillón
M C
MC
Balanzategui
A
A
Barbón
M
M
Flores
M T
MT
San Miguel
J F
JF
D000328:Adult; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D017353:Gene Deletion; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000145:classification / Q000235:genetics* / Q000401:mortality; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis
D019941:Cyclin-Dependent Kinase Inhibitor p16