title: Lack of c-kit exon 11 activating mutations in c-KIT/CD117-positive SCLC tumour specimens.
abstract: Previous studies have shown that STI571, a selective tyrosine kinase inhibitor of c-KIT, is highly effective in c-KIT/CD117-positive gastrointestinal stromal tumours (GIST), especially those that have activating mutations in the c-kit exon 11 that encodes the juxtamembrane (JM) domain of the c-KIT oncoprotein. We examined the prevalence of activating exon 11 c-kit mutations in 26 small-cell lung cancer (SCLC) cases in order to explore whether this disease is also a potential target for treatment with STI571. Expression of c-KIT, estimated by immunohistochemistry, was demonstrated in 14 out of 22 SCLC samples (64%); nine samples showed moderate to strong staining (41%), five samples were weakly positive (23%), whereas eight samples (36%) were negative for CD117. Next, we examined the mutational status of exon 11 of the c-kit gene, by single-stranded conformational polymorphism (SSCP) and sequencing in all of the cKIT/CD117-positive tumours. However, no activating mutations in the c-kit exon 11 were found by either technique. Apparently, c-KIT oncoprotein expression in SCLC was not correlated with activating mutations in c-kit exon 11. In analogy to GISTs, our results could imply that SCLC patients would not benefit from treatment with STI571.
authors.affiliation: Department of Medical Oncology, Erasmus MC, Josephine Nefkens Building (Room Be420), PO Box 1738, 3000 DR Rotterdam, The Netherlands. h.burger@erasmusmc.nl
authors.forename: H
authors.initials: H
authors.lastname: Burger
authors.forename: M A
authors.initials: MA
authors.lastname: den Bakker
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: K
authors.initials: K
authors.lastname: Nooter
mesh_terms: D018288:Carcinoma, Small Cell / Q000235:genetics*; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit