Dataset Information

Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay.

ABSTRACT: Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor-related genes. Somatic ctDNA mutations were detected in 82.8% (111/134) of patients in the total cohort. Of the 119 patients with advanced NSCLC, 27.7% (33/119) were suitable for treatment with National Comprehensive Cancer Network (NCCN) guideline-approved targeted drugs. Actionable genetic alterations included 25 EGFR mutations, 5 BRAF mutations, and 1 MET mutation, as well as 1 EML4-ALK gene fusion and 1 KIF5B-RET gene fusion. In 19.3% (23/119) of the patients, we also identified genomic alterations with that could be targeted by agents that are in clinical trials, such as mTOR inhibitors, PARP inhibitors, and CDK4/6 inhibitors. Additionally, the EGFR T790M mutation was found in 46.7% (7/15) of the patients with EGFR-TKI-resistant NSCLC, suggesting that the NGS-based ctDNA assay might be an optional method to monitor EGFR-TKI resistance and to discover mechanisms of drug resistance.

SUBMITTER: Hou H

PROVIDER: S-EPMC5668369 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay.

Hou Helei H Yang Xiaonan X Zhang Jinping J Zhang Zhe Z Xu Xiaomei X Zhang Xiaoping X Zhang Chuantao C Liu Dong D Yan Weihua W Zhou Na N Zhu Hongmei H Qian Zhaoyang Z Li Zhuokun Z Zhang Xiaochun X

Scientific reports 20171106 1

Next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assays have provided a new method of identifying tumor-driving genes in patients with advanced non-small cell lung carcinoma (NSCLC), especially in those whose cancer tissues are unavailable or in those that have acquired treatment resistance. Here, we describe a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small indels, CNVs and gene fusions in 508 tumor- ...[more]

PMID: 29097733

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Dataset Information

Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay.

Publications

Discovery of targetable genetic alterations in advanced non-small cell lung cancer using a next-generation sequencing-based circulating tumor DNA assay.

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