title: Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications.
abstract: The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n=17), smoldering multiple myeloma (SMM; n=40), and MM (n=522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 methylation does not appear to affect gene expression level. In a large cohort of patients with long-term follow-up information (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, although it was more common among patients with 17p13.1 deletions (p53 locus), a genetic progression event in MM. In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without 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.
authors.affiliation: Department of Hematology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gonzalez-Paz
authors.forename: Wee J
authors.initials: WJ
authors.lastname: Chng
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: McClure
authors.forename: Emily
authors.initials: E
authors.lastname: Blood
authors.forename: Martin M
authors.initials: MM
authors.lastname: Oken
authors.forename: Brian
authors.initials: B
authors.lastname: Van Ness
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kurtin
authors.forename: Kimberly
authors.initials: K
authors.lastname: Henderson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Ahmann
authors.forename: Morie
authors.initials: M
authors.lastname: Gertz
authors.forename: Martha
authors.initials: M
authors.lastname: Lacy
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
mesh_terms: D002453:Cell Cycle; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins