Annals of Hematology

, Volume 90, Issue 1, pp 73–79

Concurrent p16 methylation pattern as an adverse prognostic factor in multiple myeloma: a methylation-specific polymerase chain reaction study using two different primer sets

Authors

  • Geon Park
    • Department of Laboratory MedicineChosun University College of Medicine
  • Seong Ho Kang
    • Green Cross Reference Laboratory
  • Jae Hoon Lee
    • Department of Internal MedicineCachon University Gil Hospital
  • Cheolwon Suh
    • Department of Internal MedicineAsan Medical Center
  • Miyoung Kim
    • Department of Laboratory MedicineSeoul National University Hospital, Seoul National University College of Medicine
  • Seung Man Park
    • Department of Laboratory MedicineSeoul National University Hospital, Seoul National University College of Medicine
  • Tae Young Kim
    • Department of Molecular and Clinical OncologySeoul National University College of Medicine
    • Cancer Research InstituteSeoul National University College of Medicine
  • Bora Oh
    • Department of Molecular and Clinical OncologySeoul National University College of Medicine
    • Cancer Research InstituteSeoul National University College of Medicine
  • Hyun Jung Min
    • Dow Biomedica Inc.
  • Sung Soo Yoon
    • Department of Internal MedicineSeoul National University Hospital, Seoul National University College of Medicine
  • In Chul Yang
    • Center for BioanalysisKorea Research Institute of Standards and Science
  • Han Ik Cho
    • Department of Laboratory MedicineSeoul National University Hospital, Seoul National University College of Medicine
    • Korean Association of Healthy Promotion
    • Department of Laboratory MedicineSeoul National University Hospital, Seoul National University College of Medicine
    • Department of Molecular and Clinical OncologySeoul National University College of Medicine
    • Cancer Research InstituteSeoul National University College of Medicine
    • Department of Tumor BiologySeoul National University College of Medicine
  • The Korean Multiple Myeloma Working Party (KMMWP)
Original Article

DOI: 10.1007/s00277-010-1043-9

Cite this article as:
Park, G., Kang, S.H., Lee, J.H. et al. Ann Hematol (2011) 90: 73. doi:10.1007/s00277-010-1043-9

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.

Keywords

Myelomap16MethylationPrognosis

Copyright information

© Springer-Verlag 2010