NEOPLASIA Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications

The biological and clinical implications of p16 gene methylation in multiple my-eloma (MM) are still unclear despite previ-ous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in mono-clonal gammopathy of undetermined sig-nificance (MGUS; n 17), smoldering multiple myeloma (SMM; n 40), and MM (n 522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 meth-ylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up informa-tion (n 439), there was no difference in overall survival between patients with or without p16 methylation. We also found no association between p16 methylation and the main cytogenetic categories, al-though it was more common among pa-tients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no appar-ent effect on the cycle because there was also no difference in the plasma cell label-ing index (a direct measurement of prolif-eration) between patients with and with-out p16 methylation. Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences. (Blood. 2007;109:1228-1232) © 2007 by The American Society of Hematolog