Capture‐based next‐generation sequencing reveals multiple actionable mutations in cancer patients failed in traditional testing. Issue 3 (10th January 2016)

• Record Type: Journal Article
• Authors: Xie, Jing; Lu, Xiongxiong; Wu, Xue; Lin, Xiaoyi; Zhang, Chao; Huang, Xiaofang; Chang, Zhili; Wang, Xinjing; Wen, Chenlei; Tang, Xiaomei; Shi, Minmin; Zhan, Qian; Chen, Hao; Deng, Xiaxing; Peng, Chenghong; Li, Hongwei; Fang, Yuan; Shao, Yang; Shen, Baiyong
• Is Part Of: Molecular genetics & genomic medicine. Volume 4:Issue 3(2016)
• Page Start: 262
• Page End: 272
• Publication Date: 2016-01-10
• Subjects: Next‐generation sequencing -- molecular diagnosis, cancer panel -- targeted therapy; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.201
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Targeted therapies including monoclonal antibodies and small molecule inhibitors have dramatically changed the treatment of cancer over past 10 years. Their therapeutic advantages are more tumor specific and with less side effects. For precisely tailoring available targeted therapies to each individual or a subset of cancer patients, next‐generation sequencing (NGS) has been utilized as a promising diagnosis tool with its advantages of accuracy, sensitivity, and high throughput. Methods: We developed and validated a NGS‐based cancer genomic diagnosis targeting 115 prognosis and therapeutics relevant genes on multiple specimen including blood, tumor tissue, and body fluid from 10 patients with different cancer types. The sequencing data was then analyzed by the clinical‐applicable analytical pipelines developed in house. Results: We have assessed analytical sensitivity, specificity, and accuracy of the NGS‐based molecular diagnosis. Also, our developed analytical pipelines were capable of detecting base substitutions, indels, and gene copy number variations (CNVs). For instance, several actionable mutations of EGFR, PIK3CA, TP53, and KRAS have been detected for indicating drug susceptibility and resistance in the cases of lung cancer. Conclusion: Our study has shown that NGS‐based molecular diagnosis is more sensitive and comprehensive to detect genomic alterations in cancer, and supports a direct clinical use for guiding targeted therapy. Abstract : In this study, we have developed and validated a next‐generation sequencing (NGS)‐based cancer genomic diagnosis targeting hundreds of prognosis and therapeutics relevant genes on multiple types of cancer and specimen. We have assessed analytical sensitivity, specificity, and accuracy of the assay. Also, we developed clinical‐applicable analysis pipelines that are capable of detecting base substitutions, indels, and gene copy number variations (CNVs). Our study has shown that NGS‐based molecular diagnosis is more sensitive and comprehensive to detect genomic alterations in cancer, and supports a direct clinical use for guiding targeted therapy.