Clinicopathological significance of the p16 hypermethylation in multiple myeloma, a systematic review and meta-analysis.

It is well known that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of the p16 gene; however, whether or not the inactivation is associated with the clinical significance of multiple myeloma (MM) remains elusive. A meta-analysis was conducted to quantitatively determine the role of the p16 hypermethylation in the clinical significance of MM. We demonstrated that MM patients show much higher hypermethylation rates on the p16 gene in bone marrow compared to normal individuals, as well as monoclonal gammopathy of undetermined significance (MGUS). The difference of aberrant p16 hypermethylation between MM patients in advanced stage and MM patients in early stage is not statistically significant. Interestingly, the survival rate of MM patients with the p16 hypermethylation is much shorter compared to those without the p16 hypermethylation. Our results demonstrate that hypermethylation status of the p16 gene may play a role in the progression of MGUS to MM, as well as worse survival in MM. The p16 hypermethylation, which induces the loss of function of the p16 gene that plays a critical role in the early tumorigenesis of MM.