Details of delTyr mutations are summarised in Figure 1. Figure 1 Type and position of deletions including both tyrosines Tyr568 and Tyr570. GISTs with delTyr were more frequently extragastric than those with delWK (69 vs 26%, P<0.0005), whereas other clinical and tumour characteristics were not different (Table 1). After exclusion of the 8 GISTs with delTyr all targets including the 2 amino acids 557 and 558, GISTs with delTyr (n=18) were still more frequently extragastric (P=0.0031). Table 1 Clinical and pathologic characteristics of patients according to the type of exon 11 deletion Distribution of patients according to the outcome and the type of KIT exon 11 deletion is described in Figure 2. Figure 2 Distribution of the patients according to the outcome.

Relapse-free survival Mitotic count, tumour size and risk classifications were not different between patients with delWK and those with delTyr (Table 2). At the date of cut-off, median time since curative surgery was 5.1 years (range 0.4�C21.9 years). Three patients with delWK and two patients with delTyr had been included in an adjuvant prospective trial with imatinib, and were excluded of RFS analysis. Median RFS were 11.1 months (95% CI: 9.4�C66.6) and 10.8 months (95% CI: 7.1�C57.7; P=0.92; Figure 3A), respectively. Results were not modified after exclusion of the eight GISTs with delTyr including the two amino acids 557 and 558 (P=0.45). Figure 3 (A) Relapse-free survival according to the type of exon 11 deletion. (B) Progression-free survival under imatinib according to the type of exon 11 deletion.

(C) Overall survival under imatinib according to the type of exon 11 deletion. Table 2 Prognostic factors after curative surgery and outcome of patients according to the type of exon 11 deletion Objective response and survival under imatinib During follow-up, 22 patients with delWK and 14 patients with delTyr received imatinib (Figure 2). Out of these 36 patients, 26 (72%) had been included and evaluated in a prospective trial. At the date of cut-off, median time since imatinib beginning was 4.7 years (range 0.7�C6.8 years). Objective responses to imatinib were not different between patients with delWK and those with delTyr (Table 3). Median PFS under imatinib were 18.9 months (95% CI: 12.6�C ) for patients with delWK and 21.9 months (95% CI: 16.1�C37.4) for patients with delTyr (P=0.43; Figure 3B).

Median OS since imatinib beginning were 31.4 months (95% CI: 19.7�C) and 38.6 months (95% CI: 35.4�C45.3; P=0.31; Figure 3C), respectively. After exclusion of the 8 GISTs with delTyr including the two amino acids 557 and 558, results were not modified for median PFS (P=0.60) and OS (P=0.39). Table GSK-3 3 Outcome under imatinib according to the type of exon 11 deletion Discussion KIT exon 11 mutations are present in the majority of GISTs. Many different types of mutations have been published, some of which delete residues Tyr568 and Tyr570, which play an important role in KIT signal transduction.