Kun Zhang1, Min Zhang1, Jinlong Zhu1, Wang Hong1. 1. Department of Lung Cancer, The Affiliated Hospital of Military Medical Sciences, The 307th Hospital of Chinese People's Liberation Army, Beijing, China.
Abstract
OBJECTIVE: The objective of this study is to assess the gene mutation of advanced nonsmall cell lung cancer (NSCLC) patients with bone metastasis using next-generation sequencing (NGS), and screen for the driver genes which are associated with bone metastasis of lung cancer. MATERIALS AND METHODS: Eight clinicopathologic samples from advanced NSCLC combined with bone metastasis patients were collected. Exome sequencing was conducted within 483 tumor-associated genes using Hiseq 2000_PE75 NGS platform. RESULTS: Three thousand six hundred and twenty gene mutations were identified, including point mutation, insertion, and deletion. Among all genes associated with lung cancer signaling pathways, fibroblast growth factor receptor (FGFR), and cyclin-dependent kinase 12 (CDK12) were found to be mutated in all eight patients. The top three genes were FGFR, ataxia telangiectasia mutated, and CDK12, according to mutation frequency. In the meanwhile, hepatocyte nuclear factor 1 alpha, adenomatous polyposis coli, and CD22 were found to be mutated in all eight patients with an over 50% mutation frequency (75%, 62.5%, and 50%, respectively), which would be the most potential genes accounting for bone metastasis in lung cancer patients. CONCLUSION: Our findings shed light on several important signalling pathways involved in NSCLC, and suggest new potential molecular targets for treatment of NSCLC patients with bone metastasis.
OBJECTIVE: The objective of this study is to assess the gene mutation of advanced nonsmall cell lung cancer (NSCLC) patients with bone metastasis using next-generation sequencing (NGS), and screen for the driver genes which are associated with bone metastasis of lung cancer. MATERIALS AND METHODS: Eight clinicopathologic samples from advanced NSCLC combined with bone metastasispatients were collected. Exome sequencing was conducted within 483 tumor-associated genes using Hiseq 2000_PE75 NGS platform. RESULTS: Three thousand six hundred and twenty gene mutations were identified, including point mutation, insertion, and deletion. Among all genes associated with lung cancer signaling pathways, fibroblast growth factor receptor (FGFR), and cyclin-dependent kinase 12 (CDK12) were found to be mutated in all eight patients. The top three genes were FGFR, ataxia telangiectasia mutated, and CDK12, according to mutation frequency. In the meanwhile, hepatocyte nuclear factor 1 alpha, adenomatous polyposis coli, and CD22 were found to be mutated in all eight patients with an over 50% mutation frequency (75%, 62.5%, and 50%, respectively), which would be the most potential genes accounting for bone metastasis in lung cancerpatients. CONCLUSION: Our findings shed light on several important signalling pathways involved in NSCLC, and suggest new potential molecular targets for treatment of NSCLCpatients with bone metastasis.