Correlation of treatment outcome in sanger/RT‑qPCR KIT/PDGFRA wild‑type metastatic gastrointestinal stromal tumors with next‑generation sequencing results: A single‑center report.

Abstract

In patients with gastrointestinal stromal tumors (GIST), it has become mandatory to determine the driver mutation in order to predict the response to standard treatment with tyrosine kinase inhibitors (TKI). A total of 10–15% of all GIST lack activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT)/platelet-derived growth factor receptor alpha (PDGFRA) and have been classified as KIT/PDGFRA wild-type (WT) GIST. They are characterized by poor response to TKI. From a group of 119 metastatic GIST patients, 17 patients with KIT/PDGFRA/BRAF WT GIST as determined by reverse transcription-quantitative (RT-q) PCR and Sanger sequencing were profiled by a targeted next-generation sequencing (NGS) approach and their treatment outcome was assessed. In the present study, 41.2% of patients as KIT/PDGFRA/BRAF WT GIST examined with RT-qPCR and Sanger sequencing were confirmed to be carriers of pathogenic KIT/PDGFRA mutations by NGS and were responsive to TKI. The percentage of genuinely KIT/PDGFRA WT GIST in the present study thereby dropped from the initial 14.3% detected with the RT-qPCR and Sanger sequencing to 7.6% after NGS. Their outcome was universally poor. The reliability of RT-qPCR and direct Sanger sequencing results in this setting is therefore insufficient and it is recommended that NGS becomes a requirement for treatment decision at least in KIT/PDGFRA/BRAF WT GIST as determined by RT-qPCR and Sanger sequencing.