title: Circulating Tumor DNA Mutation Profiling by Targeted Next Generation Sequencing Provides Guidance for Personalized Treatments in Multiple Cancer Types.
abstract: Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.
authors.affiliation: Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Geneseeq Technology Inc., Toronto, Ontario, Canada.
authors.forename: Xue
authors.identifier: http://orcid.org/0000-0002-5567-1325
authors.initials: X
authors.lastname: Wu
authors.affiliation: Geneseeq Technology Inc., Toronto, Ontario, Canada.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Tong
authors.affiliation: Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China.
authors.forename: Liangjun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Chemoradiotherapy, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.|Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Huawu
authors.initials: H
authors.lastname: Shao
authors.affiliation: Geneseeq Technology Inc., Toronto, Ontario, Canada. yang.shao@geneseeq.com.
authors.forename: Yang W
authors.initials: YW
authors.lastname: Shao
mesh_terms: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D000066491:Clinical Decision-Making; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D057285:Precision Medicine; D057188:Workflow
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D004273:DNA, Neoplasm