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

• Published in: Journal of clinical pathology 2005-07, Vol.58 (7), p.762-765
• Main Authors: Korja, M, Finne, J, Salmi, T T, Haapasalo, H, Tanner, M, Isola, J
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Biomarkers, Tumor - metabolism; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; c-kit; Child; Child, Preschool; Chromatography, High Pressure Liquid - methods; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - metabolism; gastrointestinal stromal tumour; GIST; high performance liquid chromatography; HPLC; Humans; imatinib; Imatinib Mesylate; Infant; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Mutation; neuroblastic; neuroblastic tumour; neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - genetics; Neuroblastoma - metabolism; Original; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; PCR; Piperazines - therapeutic use; polymerase chain reaction; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Pyrimidines - therapeutic use
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2004.024331

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.