Hypermethylation of p16(ink4a) and p15(ink4b) genes as a marker of diseasein the follow-up of non-Hodgkin's lymphomas

The hypermethylation of p16ink4a and p15ink4b genes have been described as an inactivating mechanism alternative to deletions and mutations that accou nts for a relatively high proportion of cancers, including non-Hodgkin's ly mphomas (NHLs). To investigate whether detection of abnormal methylation co uld have clinical applications in the management and follow-up of lymphomas , we have analysed the behaviour and evolution of p16ink4a and p15ink4b met hylation in 13 NHL cases undergoing chemotherapy All cases were also analys ed for the presence of monoclonal rearrangements of immunoglobulin or T-cel l receptor genes. Six patients showed methylation in at least one of these genes at diagnosis, whereas in two other cases methylation appeared during the treatment. The other five cases were always unmethylated. Methylation w as detected when any histological or molecular evidence of disease was pres ent, suggesting a good correlation between methylation and disease. In some cases, we were able to detect methylation in patients at complete remissio n and without evidence of monoclonal cell population, indicating a high sen sitivity of the PCR to detect methylation. These results suggest that p16in k4a and p15ink4b methylation could be good markers of disease and could be helpful in identifying lymphoma patients at risk of relapse.