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KIT expression and methylation in medulloblastoma and PNET cell lines and tumors

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The stem cell factor/kit tyrosine kinase receptor pathway is related to tumor growth and progression in several cancers including Ewing sarcoma, a peripheral PNET (pPNET). Identifying additional groups of tumors that may use the pathway is important as they might be responsive to imatinib mesylate treatment. MB and central PNET (cPNET) are embryonal tumors of the CNS that share similar undifferentiated morphology with Ewing sarcomas and display aggressive clinical behavior. cPNET outcome is significantly lower than MB outcome, even for localized tumors treated with high-risk MB therapy. The elucidation of signaling pathways involved in MB and cPNET pathogenesis, and the discovery of new therapeutic targets is necessary to improve the treatment of these neoplasms. We analyzed KIT expression in 2 MB, one pPNET, one cPNET and 2 rhabdomyosarcoma (RMS) cell lines. Also, in 13 tumor samples (12 MB and one cPNET), we found KIT overexpression in the most aggressive cell lines (metastatic MB and pPNET). Hypermethylation of KIT was clear in the RMS non-expressing cell lines. Among MB tumors, we could see variable levels of KIT expression; a subset of them (25%) might be related in its growth pattern to KIT up-regulation. No methylated KIT was detected in the tumors expressing the lowest levels of KIT. Our results point to methylation as an epigenetic regulatory mechanism for KIT inhibition only in the KIT non-expressing RMS cell lines, and neither in the rest of the cell lines nor in the tumor samples.

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Abbreviations

CNS:

Central nervous system

EWS:

Ewing sarcoma

MB:

Medulloblastoma

MCA-Meth:

Melting curve analysis-methylation

MSP:

Methylation specific PCR

PNET:

Primitive neuroectodermal tumor

SCF:

Stem cell factor

RMS:

Rhabdomyosarcoma

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Acknowledgments

The authors are grateful to Laura Stokes for help with editing the manuscript. M. Enguita-Germán, M. Gurrea and P. Schiapparelli thank the Asociación de Amigos de la Universidad de Navarra and the Departamento de Educación del Gobierno de Navarra for the fellowships received. J.S. Castresana is grateful to the Asociación Española de Pediatría for the VIII Premio Nutribén de Investigación Pediátrica, and the Sociedad Española de Hematología y Oncología Pediátricas, Madrid. J.S. Castresana was supported in part by grants from the Departmento de Salud del Gobierno de Navarra (9/07), Caja Navarra (08/13912), and Fundación Universitaria de Navarra, Pamplona; and Fondo de Investigación Sanitaria (PI081849), Madrid. X. Fan would like to acknowledge grant support from Accelerate Brain Cancer Cure Project Award, American Brain Tumor Association Translational Grant, and Voices Against Brain Cancer Research Grant.

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Authors and Affiliations

  1. Brain Tumor Biology Unit-CIFA, University of Navarra School of Sciences, Irunlarrea 1, 31008, Pamplona, Spain

    Mónica Enguita-Germán, Mikel Gurrea, Paula Schiapparelli & Javier S. Castresana

  2. Department of Neurosurgery, University of Michigan Medical School, 109 Zina Pitcher Place, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA

    Mikel Gurrea, Thant S. Zhu, Jessica G. Crowley, Lisa L. Hamm, Mark A. Costello, Xiaobing He, Caroline E. Talsma, Callie G. Flack, Shawn L. Hervey-Jumper, Jason A. Heth, Karin M. Muraszko & Xing Fan

  3. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA

    Xing Fan

  4. Research Unit, La Paz University Hospital, Madrid, Spain

    Juan A. Rey

Authors
  1. Mónica Enguita-Germán
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  2. Mikel Gurrea
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  3. Paula Schiapparelli
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  4. Thant S. Zhu
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  5. Jessica G. Crowley
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  6. Lisa L. Hamm
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  7. Mark A. Costello
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  8. Xiaobing He
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  9. Caroline E. Talsma
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  10. Callie G. Flack
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  11. Shawn L. Hervey-Jumper
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  12. Jason A. Heth
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  13. Karin M. Muraszko
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  14. Juan A. Rey
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  15. Xing Fan
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  16. Javier S. Castresana
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Corresponding authors

Correspondence to Xing Fan or Javier S. Castresana.

Additional information

Mikel Gurrea and Paula Schiapparelli contributed equally to this work.

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Enguita-Germán, M., Gurrea, M., Schiapparelli, P. et al. KIT expression and methylation in medulloblastoma and PNET cell lines and tumors. J Neurooncol 103, 247–253 (2011). https://doi.org/10.1007/s11060-010-0391-6

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  • DOI: https://doi.org/10.1007/s11060-010-0391-6

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