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.
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.
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DOI：
10.18632/oncotarget.1906
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发表时间：
2014-04-30
期刊：
影响因子：
--
通讯作者：
Nishio K
中科院分区：
文献类型：
--
作者：
Okamoto I;Sakai K;Morita S;Yoshioka H;Kaneda H;Takeda K;Hirashima T;Kogure Y;Kimura T;Takahashi T;Atagi S;Seto T;Sawa T;Yamamoto M;Satouchi M;Okuno M;Nagase S;Takayama K;Tomii K;Maeda T;Oizumi S;Fujii S;Akashi Y;Nishino K;Ebi N;Nakagawa K;Nakanishi Y;Nishio K
从入组LETS III期试验（比较一线S-1/卡铂与紫杉醇/卡铂）的晚期NSCLC患者中采集福尔马林固定、石蜡包埋（FFPE）存档肿瘤标本，并使用Sequenom MassARRAY平台对26个基因（LungCarta Panel）中的214个体细胞热点突变和ALK、RET和ROS 1融合基因（LungFusion Panel）的20个主要变体进行多重基因分型。MET扩增通过荧光原位杂交进行评价。在48%的非鳞状细胞癌和45%的鳞状细胞癌标本中发现了至少一种基因的体细胞突变，包括EGFR（17%）、TP 53（11%）、STK 11（9.8%）、MET（7.6%）和KRAS（6.2%）。EGFR或KRAS突变分别与中位总生存期延长或缩短相关。LungFusion Panel在6例病例（2.5%）中确定了ALK融合，在5例病例（2.1%）中确定了ROS 1融合，在1例病例（0.4%）中确定了RET融合，这三种类型的重排相互排斥。发现229例患者中有9例（3.9%）为新生MET扩增阳性。与III期试验相关的NSCLC的首次多重基因分型表明，基于MassARRAY的体细胞突变和融合基因的基因检测对来自NSCLC组织FFPE标本的核酸表现良好。
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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影响因子：
82.9
作者：
Kohno T;Ichikawa H;Totoki Y;Yasuda K;Hiramoto M;Nammo T;Sakamoto H;Tsuta K;Furuta K;Shimada Y;Iwakawa R;Ogiwara H;Oike T;Enari M;Schetter AJ;Okayama H;Haugen A;Skaug V;Chiku S;Yamanaka I;Arai Y;Watanabe S;Sekine I;Ogawa S;Harris CC;Tsuda H;Yoshida T;Yokota J;Shibata T
通讯作者：
Shibata T
影响因子：
28.2
作者：
Drilon A;Wang L;Hasanovic A;Suehara Y;Lipson D;Stephens P;Ross J;Miller V;Ginsberg M;Zakowski MF;Kris MG;Ladanyi M;Rizvi N
通讯作者：
Rizvi N
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
50.5
作者：
Kim, H. R.;Lim, S. M.;Cho, B. C.
通讯作者：
Cho, B. C.
影响因子：
20.4
作者：
Takeda, Masayuki;Okamoto, Isamu;Nakagawa, Kazuhiko
通讯作者：
Nakagawa, Kazuhiko