Secondary mutation of c-kit/PDGFRα genotypes after imatinib mesylate therapy and its relationship with efficacy of sunitinib

Abstract

To investigate the relationship between secondary mutations of c-kit/PDGFRα resistance to imatinib mesylate and the efficacy of sunitinib in patients with gastrointestinal stromal tumor (GIST). Five pairs specimens were collected before and after imatinib mesylate resistance. DNA for molecular genetic investigation was extracted from formalin-fixed, paraffin-embedded tissues. Mutational analysis was performed by using PCR and direct sequencing. Five pairs of specimens were collected before and after imatinib mesylate resistance from 5 GIST patients. C-kit exon 11 mutations were detected in 3 patients, which were all acquired mutations, including c-kit exon 13 V654A, c-kit exon 13 V654E and c-kit exon 17 N822K, after imatinib mesylate resistance. Furthermore, after sunitinib treatment, 3 patients had stable disease and progression free survival (PFS) were 3.5 months, 4.4 months and 3.8 months, respectively. C-kit exon 9 mutations were detected in 2 patients with no acquired mutations after imatinib mesylate resistance. And the both had partial response from sunitinib, following with 13.1 months and 12.0 months PFS respectively. The c-kit/PDGFRα genotypes after imatinib mesylate resistance may both relate to primary mutations and efficacy of sunitinib treatment.