[EN]In order to gain further insights into the role of
the p16 gene in cell cycle regulation and the prognostic
implications of its inactivation, we investigated the methylation status of the p16 gene in 98 untreated patients using
a polymerase chain reaction assay based on the inability of
some restriction enzymes to digest methylated sequences.
Forty-one patients showed a p16 methylated gene (42%).
The percentage of S-phase plasma cells (PC) in these
patients was almost three times higher than in those with
an unmethylated p16 gene (4Æ16% ± 3Æ37% vs 1Æ5% ±
1Æ41%, P < 0Æ001). The presence of p16 methylation also
correlated with both elevated b2-microglobulin serum levels
and high C-reactive protein values. Patients with a p16
methylated gene had shorter overall and progression-free
survival than those patients without p16 methylation.
However, this feature did not retain independent prognostic
influence on multivariate analysis, probably due to its
association with the S-phase PC, which had more potent
statistical significance in the Cox model. These findings
showed methylation of the p16 gene was a frequent event
in MM patients at diagnosis, and was associated with an
increased proliferative rate of plasma cells and a poor
prognosis, indicating an important role for p16 gene in the
cell cycle regulation of multiple myeloma tumour cells, and
thus in the clinical outcome of the disease
