Pediatric and Developmental Pathology

, Volume 7, Issue 5, pp 493–498

c-kit Expression and Mutational Analysis in Medulloblastoma

  • Susan Chilton-MacNeill
  • Michael Ho
  • Cynthia Hawkins
  • Adam Gassas
  • Maria Zielenska
  • Sylvain Baruchel
Original article
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Abstract

The proto-oncogene c-kit is a receptor tyrosine kinase recognized to initiate essential signal transduction pathways that transmit biological signals for cellular proliferation, differentiation, and metastasis. Aberrant expression or mutation of c-kit has been shown to be involved in the pathogenesis of many cancers. Studies using imatinib mesylate (STI 571, Gleevec, Novartis, East Hanover, NJ, USA), an inhibitor of the tyrosine kinases brc-abl, c-kit, and PDGFR, have shown significant response in patients with chronic myelogenous leukemia and gastrointestinal stromal tumor. With the aim of identifying additional groups of tumors that may use the stem cell factor/c-kit pathway and, secondarily, may be responsive to imatinib mesylate treatment, we looked at the expression of c-kit in medulloblastoma. Medulloblastoma, a highly invasive primitive neuroectodermal tumor of the cerebellum, is the most common, malignant central nervous system tumor of childhood. Histologic features of medulloblastoma have failed to provide an accurate prediction of the clinical-biological behavior of these tumors. Characterizing the genetic events that play a role in the biology of these tumors may allow for molecular sub-typing and could lead to the development of novel therapeutic strategies. This study evaluated c-kit expression and mutational status in 10 medulloblastoma tumor samples. All 10 medulloblastoma tumors expressed c-kit by reverse transcriptase-polymerase chain reaction and 9 by immunohistochemical analysis. All tumor samples were screened for mutations in exons 9, 11, and 13 of the c-kit gene by direct sequencing. No sequence abnormalities were detected in these exons. These experiments lead us to the conclusion that c-kit activation in medulloblastoma is independent of mutation.

Keywords:

c-kit medulloblastoma imatinib mutational analysis 

Copyright information

© Society for Pediatric Pathology 2004

Authors and Affiliations

  • Susan Chilton-MacNeill
    • 1
  • Michael Ho
    • 1
  • Cynthia Hawkins
    • 1
  • Adam Gassas
    • 2
  • Maria Zielenska
    • 1
  • Sylvain Baruchel
    • 2
    • 3
  1. 1.Department of Pediatric Laboratory MedicineHospital for Sick ChildrenTorontoCanada
  2. 2.Department of Haematology/OncologyHospital for Sick ChildrenTorontoCanada
  3. 3.New Agent and Innovative Therapy ProgramHospital for Sick ChildrenTorontoCanada

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