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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

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 and Kazuto Nishio _

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Oncotarget. 2014; 5:2293-2304. https://doi.org/10.18632/oncotarget.1906

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Abstract

Isamu Okamoto1, Kazuko Sakai2, Satoshi Morita3, Hiroshige Yoshioka4, Hiroyasu Kaneda5, Koji Takeda6, Tomonori Hirashima7, Yoshihito Kogure8, Tatsuo Kimura9, Toshiaki Takahashi10, Shinji Atagi11, Takashi Seto12, Toshiyuki Sawa13, Masashi Yamamoto14, Miyako Satouchi15, Motoyasu Okuno16, Seisuke Nagase17, Koichi Takayama18, Keisuke Tomii19, Tadashi Maeda20, Satoshi Oizumi21, Shinji Fujii22, Yusaku Akashi23, Kazumi Nishino24, Noriyuki Ebi25, Kazuhiko Nakagawa5, Yoichi Nakanishi1,18 and Kazuto Nishio2

1 Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan;

2 Department of Genome Biology, Kinki University Faculty of Medicine, Osaka, Japan;

3 Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan;

4 Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan;

5 Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan;

6 Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan;

7 Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan;

8 Department of Respiratory Medicine, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan;

9 Department of Respiratory Medicine, Osaka City University Medical School, Osaka, Japan;

10 Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan;

11 Department of Respiratory Medicine, National Hospital Organization, Kinki-chuo Chest Medical Center, Osaka, Japan;

12 Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan;

13 Department of Respiratory Medicine and Oncology, Gifu Municipal Hospital, Gifu, Japan;

14 Department of Respiratory Medicine, Nagoya Ekisaikai Hospital, Nagoya, Japan;

15 Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan;

16 Department of Respiratory Medicine, Aichi Cancer Center Aichi Hospital, Okazaki, Japan;

17 Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan;

18 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;

19 Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan;

20 Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan;

21 First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan;

22 Division of Respiratory Disease, Kumamoto Regional Medical Center, Kumamoto, Japan;

23 Department of Medical Oncology, Nara Hospital Kinki University Faculty of Medicine, Nara, Japan;

24 Department of Thoracic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan;

25 Department of Respiratory Oncology, Iizuka Hospital, Fukuoka, Japan

Correspondence:

Kazuto Nishio, email:

Keywords: non–small cell lung cancer, phase III trial, genotyping, fusion gene, MET amplification

Received: February 12, 2014 Accepted: April 16, 2014 Published: April 17, 2014

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.


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