Abstract
Background: Over the last decade, substantial advances have been made in developing genotype-based target therapies for advanced NSCLC. There is an increasing need to develop high-throughput genotyping tests to evaluate larger number genetic abnormalities.Method: Archived FFPE specimens obtained at the diagnosis were available for 304 (53.9%) of the 564 patients (Pts) who were enrolled in LETS study. With the use of Sequenom's MassARRAY system, we conducted high-throughput genotyping including somatic mutations and gene fusions (ALK, ROS1 and RET). We also evaluated MET amplification by FISH.Results: A somatic mutation in at least one was identified in 105 (48%) of the 217 pts with non-squamous cell carcinoma (SCC) and 26 (45%) of the 58 pts with SCC. Overall, we identified EGFR mutations in 46 patients (17%), TP53 mutations in 30 (11%), STK11 mutations in 27 (9.8%), MET mutations in 21 (7.6%), KRAS mutations in 17 (6.2%), PIK3CA mutations in 6 (2.2%), BRAF and NRAS mutations in each 3 (1.1%), and DDR2, ERBB2, NRF2 and PTEN mutations in each one patient (0.4%). The median overall survival (OS) of EGFR mutation-positive pts was significantly longer than that of pts without EGFR mutations (23.7 v 12.6 months; P = 0.004). Conversely, pts whose tumors had KRAS mutations had a significantly shorter survival than KRAS-wild type pts (9.9 v 15.3 months; P = 0.04). LungFusion panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and RET fusion in one case (0.4%), and these three rearrangements were mutually exclusive. Among five ROS1-fusion positive patients, two patients concomitantly had KRAS mutations, and one patient had EGFRL858R and PIK3CAE542K. Nine out of 229 advanced NSCLC pts (3.9%) were identified as having de novo MET amplification.Conclusions: MassARRAY-based multiplex genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE NSCLC tissues obtained from advanced NSCLC.
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