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.
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.
Authors: H Joensuu; P J Roberts; M Sarlomo-Rikala; L C Andersson; P Tervahartiala; D Tuveson; S Silberman; R Capdeville; S Dimitrijevic; B Druker; G D Demetri Journal: N Engl J Med Date: 2001-04-05 Impact factor: 91.245
Authors: M L Lux; B P Rubin; T L Biase; C J Chen; T Maclure; G Demetri; S Xiao; S Singer; C D Fletcher; J A Fletcher Journal: Am J Pathol Date: 2000-03 Impact factor: 4.307
Authors: D E Williams; J Eisenman; A Baird; C Rauch; K Van Ness; C J March; L S Park; U Martin; D Y Mochizuki; H S Boswell Journal: Cell Date: 1990-10-05 Impact factor: 41.582
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Authors: Y Yarden; W J Kuang; T Yang-Feng; L Coussens; S Munemitsu; T J Dull; E Chen; J Schlessinger; U Francke; A Ullrich Journal: EMBO J Date: 1987-11 Impact factor: 11.598
Authors: Miikka Korja; Anne Jokilammi; Toivo T Salmi; Hannu Kalimo; Tarja-Terttu Pelliniemi; Jorma Isola; Immo Rantala; Hannu Haapasalo; Jukka Finne Journal: BMC Cancer Date: 2009-02-17 Impact factor: 4.430