title: Concurrent p16 methylation pattern as an adverse prognostic factor in multiple myeloma: a methylation-specific polymerase chain reaction study using two different primer sets.
abstract: Disruption of cell cycle control genes, including p16, is known to contribute to the cancerogenesis of multiple myeloma (MM). We investigated the methylation status of p16 and its association with common cytogenetic changes, clinicolaboratory findings, and survival in MM. Methylation-specific polymerase chain reaction was performed in 99 newly diagnosed MM patients using two different sets of primers (p16M1 and p16M2). Four patterns of p16 promoter methylation were observed: (1) concurrent methylation of p16M1 and p16M2 (P1P2), 27.3%; (2) methylation of p16M1 alone (P1N2), 7.1%; (3) methylation of p16M2 alone (N1P2), 26.3%; and (4) no methylation (N1N2), 39.4%. Patients with p16P1P1 showed shorter survivals than those with the other methylation patterns (P1N2, N1P2, or N1N2; median survival, 12 vs. 43 months; P < 0.001), regardless of the treatment protocol. In a multivariate analysis, p16P1P2 was an independent prognostic factor of adverse outcome in MM. According to International Staging System (ISS), the study population could be divided into 21.2% (20/94) for stage I, 22.3% (21/94) for stage II, and 56.4% (53/94) for stage III (P = 0.003). ISS can divide patients into prognostic groups. Of note, in patients older than 60 years, ISS was not reflective of disease stage (P = 0.114). If p16P1P2 sets up as stage 4 of ISS, modified ISS could be a more reliable staging system irrespective of age in Korean MM patients (P = 0.003 and P = 0.004 in patients younger than 60 years and in patients older than 60 years, respectively). Our study suggests the potential use of p16 methylation status in predicting the outcome of MM patients and the applicability of demethylating agents in MM.
authors: Department of Laboratory Medicine, Chosun University College of Medicine, Gwangju, South Korea.
authors: Geon
authors: G
authors: Park
authors: Seong Ho
authors: SH
authors: Kang
authors: Jae Hoon
authors: JH
authors: Lee
authors: Cheolwon
authors: C
authors: Suh
authors: Miyoung
authors: M
authors: Kim
authors: Seung Man
authors: SM
authors: Park
authors: Tae Young
authors: TY
authors: Kim
authors: Bora
authors: B
authors: Oh
authors: Hyun Jung
authors: HJ
authors: Min
authors: Sung Soo
authors: SS
authors: Yoon
authors: In Chul
authors: IC
authors: Yang
authors: Han Ik
authors: HI
authors: Cho
authors: Dong Soon
authors: DS
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000502:physiology; D004252:DNA Mutational Analysis / Q000379:methods; D017931:DNA Primers / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D013379:Substrate Specificity; D016019:Survival Analysis
chemical_list: D017931:DNA Primers