Annals of Oncology Advance Access originally published online on January 10, 2008
Annals of Oncology 2008 19(4):706-710; doi:10.1093/annonc/mdm503
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gastrointestinal tumors |
KIT and PDGFR
mutations in 104 patients with gastrointestinal stromal tumors (GISTs): a population-based study
1 Centro Regionale di Genetica Oncologica, Oncologia Medica, Ancona
2 Anatomia ed Istologia Patologica, Università Politecnica delle Marche, Ancona
3 Clinica di Oncologia Medica, Ospedali Riuniti, Ancona
4 Oncologia Medica, Ospedale Murri, Jesi
5 Oncologia Medica, Ospedale di Fermo, Fermo
6 Oncologia Medica, Ospedale di Macerata, Macerata, Italy
7 Department of Internal Medicine, Ohio State University, Columbus, OH, USA
8 Scuola di Specializzazione in Oncologia, Università Politecnica delle Marche, Ancona, Italy
9 Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH, USA
* Correspondence to: Dr C. Braconi, Centro Regionale di Genetica Oncologica, Oncologia Medica, Università Politecnica delle Marche, via Tronto 1, 60126 Ancona, Italy. Tel: +39-71-2205161; Fax: +39-71-2206191; E-mail: chiarabraconi{at}tiscali.it
Background: The prognostic significance of KIT or platelet-derived growth factor receptor 
(PDGFR) mutations in gastrointestinal stromal tumors (GISTs) is still controversial.
Patients and methods: In all, 104 patients were diagnosed with GISTs by KIT immunoreactivity; tumor DNA was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17 and in PDGFR exons 12 and 18. Disease-free survival (DFS) was analyzed in 85 radically resected patients.
Results: KIT mutations occurred in exon 11 (69), in exon 9 (11) and in exon 17 (1). PDGFR mutations were detected in exon 18 (10) and in exon 12 (3). Ten GISTs were wild type. Exon 11 mutations were as follows: deletions in 42 cases and point mutations in 20 cases and insertions and duplications, respectively, in 2 and 5 cases. A better trend in DFS was evident for duplicated and point-mutated exon 11 KIT GISTs. There was a significant association between PDGFR mutations, gastric location and lower mitotic index. Moreover, PDGFR-mutated GISTs seemed to have a better outcome.
Conclusions: Point mutations and duplications in KIT exon 11 are associated with a better clinical trend in DFS. PDGFR-mutated GISTs are preferentially localized in the stomach and seem to have a favorable clinical behavior.
Key words:
GISTs, KIT, mutations, PDGFR, prognosis
Received for publication August 29, 2007. Revision received September 25, 2007. Accepted for publication September 28, 2007.