B. Martinez-delgado et al., Hypermethylation of p16(ink4a) and p15(ink4b) genes as a marker of diseasein the follow-up of non-Hodgkin's lymphomas, BR J HAEM, 109(1), 2000, pp. 97-103
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.