We also found no association between p16 methylation and the main cytogenetic categories, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM.
In 32 cases of multiple myeloma and 19 cases of MGUS, significantly more frequent methylation of p16 (p = 0.001), SHP1 (p< or =0.001) and E-cadherin (p< or =0.001) genes was found in multiple myeloma than in MGUS.
As regards p16 methylation, we confirmed a high prevalence of p16 methylation (40%) in patients affected by MM and demonstrated that MTHFR 677CC is associated with a higher prevalence of p16 hypermethylation.
Therefore, p16 methylation seems to have no correlation with angiogenesis and VEGF expression, neither with overall and event-free survival in MM patients.
Since the incidence and clinical implications of abnormalities of TP53, CDKN2A (encoding for p16 and p14) and MDM2 genes (chromosome 12) in multiple myeloma (MM) is not clear, we investigated allelic loss at the former two loci and gain at the latter locus in a series of 82 MM patients.
To examine the function of p18 as a putative tumor suppressor in myeloma cells, a zinc-inducible p18 construct was stably transfected into KMS12, a MM cell line with biallelic p18 and monoallelic p16 deletions as well as cyclin D1 overexpression.
p16 gene methylation was detected in 6 of 55 patients (10.9%), who were 1 patient with M2a, 1 patient with M5a, 2 patients with chronic myelogenous leukemia (CML) in blast crisis, 1 patient with progressing multiple myeloma (MM), 1 with non-Hodgkin's lymphoma (NHL) accompanied by B-ALL, respectively. p16 gene methylation correlates with adverse prognostic features.
These results suggest that inactivation of the p16 gene by methylation may be associated with decreased growth control and the development of PCL in a subset of patients with MM.