Lack of c-kit exon 11 activating mutations in c-KIT/CD117-positive SCLC tumour specimens

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 o...

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Bibliographic Details
Published in:European journal of cancer (1990) 2003-04, Vol.39 (6), p.793-799
Main Authors: Burger, H., den Bakker, M.A., Stoter, G., Verweij, J., Nooter, K.
Format: Article
Language:English
Subjects:
Biological and medical sciences
c-KIT/CD117
Carcinoma, Small Cell - genetics
Exon 11 activating mutations
Exons
Humans
Immunohistochemistry
Juxtamembrane domain
Lung Neoplasms - genetics
Medical sciences
Mutation - genetics
Pneumology
Polymerase Chain Reaction - methods
Proto-Oncogene Proteins c-kit - genetics
Small-cell lung cancer
SSCP
STI571
Tumors of the respiratory system and mediastinum
Tyrosine kinase receptor/inhibitor
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Summary: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.
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(03)00026-1