Identification of enriched driver gene alterations in subgroups of non-small cell lung cancer patients based on histology and smoking status

Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. Patients with primary lung cancer who underwent cl...

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Bibliographic Details
Published in:PloS one 2012-06, Vol.7 (6), p.e40109-e40109
Main Authors: An, She-Juan, Chen, Zhi-Hong, Su, Jian, Zhang, Xu-Chao, Zhong, Wen-Zhao, Yang, Jin-Ji, Zhou, Qing, Yang, Xue-Ning, Huang, Ling, Guan, Ji-Lin, Nie, Qiang, Yan, Hong-Hong, Mok, Tony S, Wu, Yi-Long
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adult
Aged
Aged, 80 and over
Alterations
Analysis
Biomarkers
Cancer
Cancer genetics
Cancer therapies
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Care and treatment
Chemotherapy
Clinical trials
Computer memory
Consortia
Epidermal growth factor
Epidermal growth factor receptors
Female
Fibroblast growth factor receptor 2
Gene amplification
Gene sequencing
Genes
Genes, Neoplasm - genetics
Genetic aspects
Genetic Predisposition to Disease
Genetic screening
Genetic testing
Histology
Humans
K-Ras protein
Lung cancer
Lung diseases
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical prognosis
Medical research
Medicine
Middle Aged
Mutation
Mutation - genetics
Mutation Rate
Non-small cell lung cancer
Non-small cell lung carcinoma
Oncology
Patients
PTEN protein
Receptor, Epidermal Growth Factor - genetics
Small cell lung cancer
Smokers
Smoking
Smoking - genetics
Squamous cell carcinoma
Statistical analysis
Subgroups
Survival Analysis
Young Adult
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Description
Summary:Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0040109