Annals of Hematology

, Volume 90, Issue 1, pp 73–79 | Cite as

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

  • Geon Park
  • Seong Ho Kang
  • Jae Hoon Lee
  • Cheolwon Suh
  • Miyoung Kim
  • Seung Man Park
  • Tae Young Kim
  • Bora Oh
  • Hyun Jung Min
  • Sung Soo Yoon
  • In Chul Yang
  • Han Ik Cho
  • Dong Soon Lee
  • The Korean Multiple Myeloma Working Party (KMMWP)
Original Article

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

Myeloma p16 Methylation Prognosis 

Notes

Acknowledgement

This work was supported in part by (1) the National R&D Program for Cancer Control, Ministry of Health, Welfare and Family Affairs, Republic of Korea (0720440), and (2) the Korea Science and Engineering Foundation (KOSEF) funded by the Ministry of Education, Science, and Technology (20100020584). Tae Young Kim and Bora Oh are grateful for being awarded a BK21 fellowship.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Geon Park
    • 1
  • Seong Ho Kang
    • 2
  • Jae Hoon Lee
    • 3
  • Cheolwon Suh
    • 4
  • Miyoung Kim
    • 5
  • Seung Man Park
    • 5
  • Tae Young Kim
    • 6
    • 7
  • Bora Oh
    • 6
    • 7
  • Hyun Jung Min
    • 8
  • Sung Soo Yoon
    • 9
  • In Chul Yang
    • 10
  • Han Ik Cho
    • 5
    • 11
  • Dong Soon Lee
    • 5
    • 6
    • 7
    • 12
  • The Korean Multiple Myeloma Working Party (KMMWP)
  1. 1.Department of Laboratory MedicineChosun University College of MedicineGwangjuSouth Korea
  2. 2.Green Cross Reference LaboratoryYong-InSouth Korea
  3. 3.Department of Internal MedicineCachon University Gil HospitalIncheonSouth Korea
  4. 4.Department of Internal MedicineAsan Medical CenterSeoulSouth Korea
  5. 5.Department of Laboratory MedicineSeoul National University Hospital, Seoul National University College of MedicineSeoulSouth Korea
  6. 6.Department of Molecular and Clinical OncologySeoul National University College of MedicineSeoulSouth Korea
  7. 7.Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  8. 8.Dow Biomedica Inc.SeoulSouth Korea
  9. 9.Department of Internal MedicineSeoul National University Hospital, Seoul National University College of MedicineSeoulSouth Korea
  10. 10.Center for BioanalysisKorea Research Institute of Standards and ScienceDaejeonSouth Korea
  11. 11.Korean Association of Healthy PromotionSeoulSouth Korea
  12. 12.Department of Tumor BiologySeoul National University College of MedicineSeoulSouth Korea

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