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Updated: Aug 20, 2026
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
C-kit expression and mutational analysis in medulloblastoma
Susan Chilton-Macneill1, Michael Ho, Cynthia Hawkins
1Department of Pediatric Laboratory Medicine, Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, ON, Canada.
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 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.
Insights
Proto-oncogene c-kit is expressed in medulloblastoma, a common childhood brain tumor. Its activation in these tumors occurs independently of mutations, suggesting alternative therapeutic targets beyond direct c-kit inhibition.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The proto-oncogene c-kit encodes a receptor tyrosine kinase crucial for cell signaling in proliferation, differentiation, and metastasis.
- Aberrant c-kit expression or mutations are implicated in various cancers, with imatinib mesylate showing efficacy in certain tyrosine kinase-driven tumors.
- Medulloblastoma, a malignant pediatric central nervous system tumor, requires better characterization for targeted therapies.
Purpose of the Study:
- To investigate c-kit expression and mutational status in medulloblastoma.
- To determine if the stem cell factor/c-kit pathway is involved in medulloblastoma pathogenesis.
- To explore potential responsiveness of medulloblastoma to imatinib mesylate.
Main Methods:
- Analysis of c-kit expression in 10 medulloblastoma samples using reverse transcriptase-polymerase chain reaction and immunohistochemistry.
- Screening for mutations in exons 9, 11, and 13 of the c-kit gene via direct sequencing.
Main Results:
- All 10 medulloblastoma samples expressed c-kit mRNA.
- Immunohistochemical analysis confirmed c-kit expression in 9 out of 10 tumors.
- No mutations were detected in the screened exons (9, 11, and 13) of the c-kit gene.
Conclusions:
- Medulloblastoma tumors express c-kit.
- c-kit activation in medulloblastoma is independent of mutations in the analyzed exons.
- This suggests that therapeutic strategies targeting c-kit in medulloblastoma may need to consider mechanisms other than direct mutation-induced activation.
