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

Mónica Enguita-Germán, Mikel Gurrea, Paula Schiapparelli, 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, Juan A. Rey, Xing Fan, Javier S. Castresana

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalJournal of neuro-oncology
Volume103
Issue number2
DOIs
StatePublished - Jun 2011

Keywords

  • KIT
  • Medulloblastoma
  • Methylation
  • PNET
  • Stem cell factor

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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