title: 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.affiliation: Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.forename: Koji
authors.initials: K
authors.lastname: Takeda
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirashima
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kogure
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kimura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Atagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Okuno
authors.forename: Seisuke
authors.initials: S
authors.lastname: Nagase
authors.forename: Koichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.forename: Tadashi
authors.initials: T
authors.lastname: Maeda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujii
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Akashi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nishino
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ebi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004252:DNA Mutational Analysis; D004338:Drug Combinations; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D009154:Mutation; D010094:Oxonic Acid / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D016190:Carboplatin; D017239:Paclitaxel