C10 - Study of mutational status of Sicilian GISTs patients

Abstract

Background: Gastrointestinal Stromal Tumors (GISTs) are the most frequent mesenchymal tumors of the GI tract. The discovery of kinase mutations has changed the natural course of GISTs and the response to tyrosine kinase inhibitors is indeed determined by the type of mutation.Table 1 : C10ExonNumber and Mutation type1139 deletion19 substitution9 insertion2 complex mutation99 duplication1 substitution1 deletion122 substitution2 deletion184 substitution2 insertion Open table in a new tab Table 2 : C10Our StudyLiterature dataKIT (tot)69.5%75%-Exon 1158.5%65%-Exon 910%8%-Exon 131%1%PDGFRA (tot)8.5%10%-Exon 123.5%2%-Exon 185%8%WT22%15% Open table in a new tab Approximately 75% of all GISTs have c-KIT activating mutations, most frequently exon 11 (75%) and exon 9 (7-10%);10% have PDGFRA mutations (exon 12-14-18) and 15% do not have a detectable mutation in KIT or PDGFRA (wild-type). The aim of the study is to assess the mutational characteristics of a Sicilian GIST patient series and to compare it with literature data. Material and methods: 152 patients, were followed from June 2008 to date in UOC of Oncology at the University Hospital of Palermo. Study population evaluable is composed by 118 patients. DNA from paraffin-embedded tumor tissue is obtained through the QIAmp DNA FFPE Tissue kit. Mutational analysis is obtained by Genetic Analyzer ABI 3130xl and data analysis are performed through Sequencing Analysis software v3.2. Results: Of the 118 patients evaluated (39% women; 61% man), 82 patients have c-KIT mutations (69.5%), 10 patients have PDGFRa mutations (8.5%) and 26 patients are wild-type (22%). Among the series of c-KIT mutated patients we have identified 4 cases of LOH (Loss of Heterozigosity). The type of mutation found is shown in Table 1. The mutation frequency in different exons and the comparison with the data of the literature is specified in Table 2. Conclusions: Our data show a frequency of KIT mutations lower than that reported in the literature (69.5% vs 75%); in particular it is less frequent mutation of exon 11 and appears slightly more frequently mutation of exon 9. Mutation rate in PDGFRa reflects data reported in literature. In our series the number of WT is higher and we are currently evaluating the presence of other alterations (e.g. BRAF, KRAS). The relative mutation type of PDGFRA and KIT genes is in line with other studies, with prevalence of deletions in KIT exon 11, and duplication in KIT exon 9.