TY - JOUR
T1 - Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin
T2 - Results of a West Japan Oncology Group study
AU - Okamoto, Isamu
AU - Sakai, Kazuko
AU - Morita, Satoshi
AU - Yoshioka, Hiroshige
AU - Kaneda, Hiroyasu
AU - Takeda, Koji
AU - Hirashima, Tomonori
AU - Kogure, Yoshihito
AU - Kimura, Tatsuo
AU - Takahashi, Toshiaki
AU - Atagi, Shinji
AU - Seto, Takashi
AU - Sawa, Toshiyuki
AU - Yamamoto, Masashi
AU - Satouchi, Miyako
AU - Okuno, Motoyasu
AU - Nagase, Seisuke
AU - Takayama, Koichi
AU - Tomii, Keisuke
AU - Maeda, Tadashi
AU - Oizumi, Satoshi
AU - Fujii, Shinji
AU - Akashi, Yusaku
AU - Nishino, Kazumi
AU - Ebi, Noriyuki
AU - Nakagawa, Kazuhiko
AU - Nakanishi, Yoichi
AU - Nishio, Kazuto
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
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U2 - 10.18632/oncotarget.1906
DO - 10.18632/oncotarget.1906
M3 - Article
C2 - 24810493
AN - SCOPUS:84899533736
VL - 5
SP - 2293
EP - 2304
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 8
ER -
