No GIST-type c-kit gain of function mutations in neuroblastic tumours.
OBJECTIVE
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.
Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
M
M
Korja
J
J
Finne
T T
TT
Salmi
H
H
Haapasalo
M
M
Tanner
J
J
Isola
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D009154:Mutation; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit