ORIGINAL ARTICLE

No GIST-type c-kit gain of function mutations in neuroblastic tumours

M Korja¹, J Finne¹, T T Salmi², H Haapasalo³, M Tanner⁵ and J Isola⁴

¹ Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland
² Department of Paediatrics, Turku University Central Hospital, Turku, FI-20520 Finland
³ Department of Pathology, Tampere University Hospital, FI-33521 Tampere, Finland
⁴ Laboratory of Cancer Biology, Institute of Medical Technology, University of Tampere and Tampere University Hospital, FI-33014 Tampere, Finland
⁵ Department of Oncology, Tampere University Hospital, FI-33520

Correspondence to:
Correspondence to:
Dr M Korja
Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland; miikka.korja{at}utu.fi

Aims: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment.

Methods: Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC).

Results: Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs.

Conclusions: c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated.

Abbreviations: GIST, gastrointestinal stromal tumour; HPLC, high performance liquid chromatography; NT, neuroblastic tumour; PCR, polymerase chain reaction

Keywords: c-kit; gastrointestinal stromal tumour; neuroblastoma; neuroblastic; imatinib

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