Subtype-specific expression and genetic alterations of the chemokine receptor gene CXCR4 in medulloblastomas

Ulrich Schüller, Arend Koch, Wolfgang Hartmann, Maria L. Garrè, Cynthia G. Goodyer, Armando Cama, Niels Sörensen, Otmar D. Wiestler, Torsten Pietsch

Research output: Contribution to journalArticlepeer-review

Abstract

Recent findings indicate that the chemokine receptor Cxcr4 is essential for normal development of the cerebellar cortex. As medulloblastomas (MBs), the most common malignant brain tumors of childhood, are believed to arise from neuronal cerebellar precursors, we asked whether there is a potential role for Cxcr4 in the pathogenesis of MB. RT-PCR and immunohistochemistry revealed expression of Cxcr4 in different variants of MBs. Whereas 18/20 classic MBs showed very low levels of CXCR4 mRNA, high amounts were expressed in 17/18 desmoplastic and 6/7 extensively nodular MBs. In addition, a significant correlation of high CXCR4 mRNA levels and presence of the neurotrophin receptor p75N1R or expression of ATOH1 and GLI1 suggests that CXCR4 is a reliable marker for tumors derived from the cerebellar external granular layer. Because Cxcr4 is important for migration and cell cycle control of granular precursors, we screened for mutations in the coding region by SSCP and gene sequencing. In a series of 90 MBs and 8 MB cell lines, we found one germline and one somatic mutation resulting in amino acid substitutions in the first (Ile53Leu) and second (Asp97Asn) transmembrane regions, respectively. These data suggest that Cxcr4 may be involved in the pathogenesis of MBs.

Original languageEnglish
Pages (from-to)82-89
Number of pages8
JournalInternational Journal of Cancer
Volume117
Issue number1
DOIs
Publication statusPublished - Oct 20 2005

Keywords

  • Cerebellum
  • CXCR4
  • External granule cell layer
  • Medulloblastoma
  • SDF-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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