Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study.

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.

• Authors: Isamu Okamoto, Kazuko Sakai, Satoshi Morita, Hiroshige Yoshioka, Hiroyasu Kaneda, Koji Takeda, Tomonori Hirashima, Yoshihito Kogure, Tatsuo Kimura, Toshiaki Takahashi, Shinji Atagi, Takashi Seto, Toshiyuki Sawa, Masashi Yamamoto, Miyako Satouchi, Motoyasu Okuno, Seisuke Nagase, Koichi Takayama, Keisuke Tomii, Tadashi Maeda, Satoshi Oizumi, Shinji Fujii, Yusaku Akashi, Kazumi Nishino, Noriyuki Ebi, Kazuhiko Nakagawa, Yoichi Nakanishi, Kazuto Nishio
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 8 Pg. 2293-304 (Apr 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 24810493 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality)
• DNA Mutational Analysis
• Drug Combinations
• Female
• Gene Expression Profiling (methods)
• Humans
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, genetics, mortality)
• Male
• Mass Spectrometry
• Middle Aged
• Multiplex Polymerase Chain Reaction (methods)
• Mutation
• Oxonic Acid (administration & dosage)
• Paclitaxel (administration & dosage)
• Tegafur (administration & dosage)