Lung Adenocarcinomas with HER2-Activating Mutations Are Associated with Distinct Clinical Features and HER2/EGFR Copy Number Gains
文献类型：期刊论文
| 作者 | Li, CG; Sun, YH; Fang, R; Han, XK; Luo, XY; Wang, R; Pan, YJ; Hu, HC; Zhang, Y; Pao, W |
| 刊名 | JOURNAL OF THORACIC ONCOLOGY
 |
| 出版日期 | 2012 |
| 卷号 | 7期号:1页码:85-89 |
| 关键词 | HER2 Lung adenocarcinoma Mutation Copy number EGFR KRAS |
| 通讯作者 | Chen, HQ (reprint author), Fundan Univ, Shanghai Canc Ctr, Dept Thorac Surg, 270 Dong An Rd, Shanghai 200032, Peoples R China.,shenleijin@yahoo.com ; hbji@sibs.ac.cn ; hqchen1@yahoo.com |
| 英文摘要 | Introduction: A fraction of lung adenocarcinomas harbor activating mutations in the HER2 kinase domain. HER2-targeted therapies have shown minimal benefit in molecularly unselected patients. We investigated clinical and potential molecular factors associated with HER2-mutant lung adenocarcinoma. Methods: A total of 224 lung adenocarcinoma samples were examined for activating mutations in epidermal growth factor receptor (EGFR; exons 18-22), V-Ki-ras2 Kirsten rat sarcoma (KRAS; exons 2 and 3), and HER2 (exons 18-21) by direct sequencing. Gene copy number and protein expression of both EGFR and HER2 were further explored in samples harboring HER2 mutations using fluorescence in situ hybridization and immunohistochemistry, respectively. Results: The mutation rates of EGFR, KRAS, HER2 were 63.39% (142/224), 4.46% (10/224), and 3.57% (8/224), respectively. All mutations were mutually exclusive. All eight HER2 mutations occurred in never smokers and seven were in women. The HER2 mutation rate in samples without EGFR and KRAS mutations was 11.11% (8/72). Seven of eight HER2-mutated tumors showed HER2 copy number gains (CNGs) and five showed EGFR CNGs. All of the HER2-mutated samples showed either HER2 or EGFR CNGs. Gene amplification of HER2 and EGFR was mutually exclusive in HER2-mutated samples. Conclusion: HER2 mutations in lung adenocarcinoma predominantly occurred in women and never smokers. Most HER2-mutated tumors showed HER2 CNGs. As all of the samples with HER2 mutation showed either HER2 or EGFR CNGs, these patients could potentially benefit from novel EGFR/HER2 dual or pan-erythroblastic leukemia viral oncogene homolog tyrosine kinase inhibitors. |
| 学科主题 | Oncology; Respiratory System |
| 类目[WOS] | Oncology ; Respiratory System |
| 关键词[WOS] | TYROSINE KINASE INHIBITORS ; IN-SITU-HYBRIDIZATION ; IRREVERSIBLE EGFR ; SOMATIC MUTATIONS ; CANCER-PATIENTS ; ONCOLOGY-GROUP ; GEFITINIB ; HER2 ; GENE ; TRASTUZUMAB |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000300305600014 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/533]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Li, CG,Sun, YH,Fang, R,et al. Lung Adenocarcinomas with HER2-Activating Mutations Are Associated with Distinct Clinical Features and HER2/EGFR Copy Number Gains[J]. JOURNAL OF THORACIC ONCOLOGY,2012,7(1):85-89. |
| APA | Li, CG.,Sun, YH.,Fang, R.,Han, XK.,Luo, XY.,...&Chen, HQ.(2012).Lung Adenocarcinomas with HER2-Activating Mutations Are Associated with Distinct Clinical Features and HER2/EGFR Copy Number Gains.JOURNAL OF THORACIC ONCOLOGY,7(1),85-89. |
| MLA | Li, CG,et al."Lung Adenocarcinomas with HER2-Activating Mutations Are Associated with Distinct Clinical Features and HER2/EGFR Copy Number Gains".JOURNAL OF THORACIC ONCOLOGY 7.1(2012):85-89. |
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