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

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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.

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Acknowledgments

We are grateful to all the professionals who referred samples for these studies. We would also like to thank Desiree Ramal for her valuable help in the data manager task. English text was revised by the translation services of Fundación para la Investigación Hospital La Fe.

Conflict of interest statement

No conflict of interest has been declared.

Author information

Authors and Affiliations

  1. Unidad de Genética y Diagnóstico Prenatal, Edificio de Anatomia Patologica, Hospital Universitario La Fe, Av/Campanar Nº21, 46009, Valencia, Spain

    E. Grau, F. Martinez, C. Orellana & S. Oltra

  2. CIBER de Enfermedades Raras (CIBERER), Madrid, Spain

    E. Grau

  3. Servicio de Oncología Pediátrica, Hospital Universitario La Fe, Valencia, Spain

    A. Canete, Y. Yañez & V. Castel

  4. Servicio de Anatomía Patológica, Hospital Universitario La Fe, Valencia, Spain

    R. Noguera

  5. Departamento de Patología, Universidad de Valencia, Valencia, Spain

    M. Hernandez

  6. Departamento de Estadística e I.O., Universidad de Valencia, Valencia, Spain

    J. D. Bermúdez

Authors
  1. E. Grau
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  2. F. Martinez
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  3. C. Orellana
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  4. A. Canete
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  5. Y. Yañez
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  6. S. Oltra
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  7. R. Noguera
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  8. M. Hernandez
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  9. J. D. Bermúdez
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  10. V. Castel
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Corresponding author

Correspondence to E. Grau.

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Grau, E., Martinez, F., Orellana, C. et al. Epigenetic alterations in disseminated neuroblastoma tumour cells: influence of TMS1 gene hypermethylation in relapse risk in NB patients. J Cancer Res Clin Oncol 136, 1415–1421 (2010). https://doi.org/10.1007/s00432-010-0796-9

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  • DOI: https://doi.org/10.1007/s00432-010-0796-9

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