title: Noninvasive diagnosis and monitoring of mutations by deep sequencing of circulating tumor DNA in esophageal squamous cell carcinoma.
abstract: Circulating tumor DNA (ctDNA) is becoming an important biomarker in noninvasive diagnosis and monitoring of tumor dynamics. This study tested the feasibility of plasma ctDNA for the non-invasive analysis of tumor mutations in esophageal squamous cell carcinoma (ESCC) by sequencing of tumor, tumor-adjacent, and normal tissue, as well as pre-surgery and post-surgery plasma. Exome sequencing of eight patients identified between 29 and 134 somatic mutations in ESCCs, many of which were also determined in ctDNA. Comparison of pre-surgery and post-surgery plasma has shown that mutations had reduced frequency or disappeared after surgery treatment. We further evaluated the TruSight Cancer sequencing panel by using it to detect mutations in the plasma of three patients. Tumor mutations were only found in one of them. To design a sequencing panel with improved targeting, we identified significantly mutated genes by meta-analysis of 532 ESCC genomes. Our results confirmed the well-known driver genes and found several uncharacterized genes. The new panel consisted of 90 recurrent genes, which theoretically achieved 94% and 75% of sensitivity when detecting at least 1 and 2 mutant genes in ESCC patients, respectively. Our results demonstrate the feasibility of using ctDNA to detect ESCCs and monitor treatment effect. The low-cost and sensitive target panel could facilitate clinical usage of ctDNA as a noninvasive biomarker.
authors.affiliation: Department of Radiotherapy, Huai'an First People's Hospital, Huai'an, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Luo
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Hongjin
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Ding
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Basepair Biotechnology, Co.,Ltd, Suzhou, China.
authors.forename: Dongkai
authors.initials: D
authors.lastname: Wei
authors.affiliation: Basepair Biotechnology, Co.,Ltd, Suzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address: yxli@sibs.ac.cn.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China. Electronic address: wushixiu@medmail.com.cn.
authors.forename: Shixiu
authors.initials: S
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D000077277:Esophageal Squamous Cell Carcinoma; D052138:Genes, Neoplasm; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: Diagnosis; Esophageal squamous cell carcinoma; Sequencing; ctDNA