Journal of Cancer Research and Clinical Oncology

, Volume 136, Issue 9, pp 1415–1421

Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of TMS1 gene hypermethylation in relapse risk in NB patients

  • E. Grau
  • F. Martinez
  • C. Orellana
  • A. Canete
  • Y. Yañez
  • S. Oltra
  • R. Noguera
  • M. Hernandez
  • J. D. Bermúdez
  • V. Castel
Original Paper

DOI: 10.1007/s00432-010-0796-9

Cite this article as:
Grau, E., Martinez, F., Orellana, C. et al. J Cancer Res Clin Oncol (2010) 136: 1415. doi:10.1007/s00432-010-0796-9

Abstract

Purpose

Most neuroblastoma patients over 18 months of age at diagnosis present disseminated disease. The presence of neuroblastoma cells in bone marrow can be used to evaluate the response to treatment. It is possible that alterations in certain tumour cells might confer a selective advantage over tumour dissemination process, and probably be helpful in the clonal selection of tumour-specific cells that could originate metastasis.

Methods

We performed real-time quantitative PCR to identify the presence of disseminated tumour cells in bone marrow samples, and we used MSP to analyse the methylation profile of 20 genes putatively implied in dissemination.

Results

We described epigenetic alterations in the methylated status of certain genes in disseminated tumour cells from bone marrow. Those cases with high rate of hypermethylation showed an increased probability of relapse during or after treatment. We found significantly poor prognosis in event-free survival in cases with hypermethylation of TMS1, MGMT and RARβ2 genes.

Conclusion

We could not confirm the presence of a specific methylation profile in disseminated neuroblastoma tumour cells, but a high accumulation of epigenetic events in those cells is associated with a high risk of relapse, independently of MYCN amplification.

Keywords

Neuroblastoma Methylation Prognosis factor Disseminated disease Metastasis TMS1 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • E. Grau
    • 1
    • 2
  • F. Martinez
    • 1
  • C. Orellana
    • 1
  • A. Canete
    • 3
  • Y. Yañez
    • 3
  • S. Oltra
    • 1
  • R. Noguera
    • 4
  • M. Hernandez
    • 5
  • J. D. Bermúdez
    • 6
  • V. Castel
    • 3
  1. 1.Unidad de Genética y Diagnóstico Prenatal, Edificio de Anatomia PatologicaHospital Universitario La FeValenciaSpain
  2. 2.CIBER de Enfermedades Raras (CIBERER)MadridSpain
  3. 3.Servicio de Oncología PediátricaHospital Universitario La FeValenciaSpain
  4. 4.Servicio de Anatomía PatológicaHospital Universitario La FeValenciaSpain
  5. 5.Departamento de PatologíaUniversidad de ValenciaValenciaSpain
  6. 6.Departamento de Estadística e I.O.Universidad de ValenciaValenciaSpain

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