C-kit expression and mutational analysis in medulloblastoma

Pediatr Dev Pathol. 2004 Sep-Oct;7(5):493-8. doi: 10.1007/s10024-004-1116-7. Epub 2004 Jul 30.


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 Hannover, 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.

MeSH terms

  • Adolescent
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / metabolism*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism*
  • Mutation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-kit / genetics*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction


  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RNA, Messenger
  • Proto-Oncogene Proteins c-kit