Next generation sequencing (NGS) in wild type GISTs.

Abstract

e22507 Background: The majority driven mutation of GIST are located in KIT and PDGFRA. A proportion of the remaining 10% of GIST without KIT or PDGFRA mutations called wild type GIST (wt-GIST). It is poor response to imatinib, sunitinib or regorafenib in these wt-GIST patients. It is lack of precise drug target of wt-GIST. We analyzed next generation exome sequencing (NGS) results in wt-GISTs. Methods: Whole exome sequencing was performed on freezing tumor tissue and peripheral blood DNA with 100X sequencing depth. The low frequency somatic mutation was confirmed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and Sanger sequencing. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: A total of 11 wt-GIST samples were analyzed. ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) was mutated in one CD117 negative patients with 5.3% mutation frequency of c. 364G > A (p. A122T). Sanger sequencing couldn’t found the ROS1 mutated in tumor tissue. But this low frequency somatic mutation was verified by MALDI-TOF. Conclusions: This is the first report showed a new ROS1 somatic mutation in wt-GIST. Our results indicated that ROS1 could be a new possible driven mutation in wt-GIST. ROS1 rearrangement have been described in a subset of non-small-cell lung cancers (NSCLC). Crizotinib shows a potent curative effect in ROS1 rearrangement NSCLC. Therefore, crizotinib might be an appropriate drug to GIST patients with mutated ROS1.