Abstract
Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.
Highlights
Lung cancer is the leading cause of death related to cancer worldwide,with non–small cell lung cancer (NSCLC) accounting for 85% of lung cancer cases [1]
FFPE specimens obtained at diagnosis were available for 304 (53.9%) of the 564 patients enrolled in the Lung Cancer Evaluation of TS-1 (LETS) study
Collection of tumor material was not mandatory in the LETS study, FFPE archival tumor specimens were obtained from more than half of the advanced NSCLC patients enrolled in the study
Summary
Lung cancer is the leading cause of death related to cancer worldwide,with non–small cell lung cancer (NSCLC) accounting for 85% of lung cancer cases [1]. The subsequent discovery of ROS1 and RET rearrangements as potentially treatable targets suggested that several chromosomal translocations and corresponding gene fusions may serve as a driving force for NSCLC [12,13,14,15,16]. These findings have highlighted the genetic diversity of NSCLC, which can no longer be considered a single disease. The clinical implementation of genomic profiling for NSCLC with high-throughput and multiplex genotyping tests is warranted in order to prioritize appropriate therapies for individual patients [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
