title: Cell-Free DNA Provides a Good Representation of the Tumor Genome Despite Its Biased Fragmentation Patterns.
abstract: Cell-free DNA (cfDNA) is short, extracellular, fragmented double-stranded DNA found in plasma. Plasma of patients with solid tumor has been found to show significantly increased quantities of cfDNA. Although currently poorly understood, the mechanism of cfDNA generation is speculated to be a product of genomic DNA fragmentation during cellular apoptosis and necrosis. Sequencing of cfDNA with tumor origin has identified tumor biomarkers, elucidating molecular pathology and assisting in accurate diagnosis. In this study, we performed whole-genome sequencing ofcfDNA samples with matching tumor and whole blood samples from five patients diagnosed with stage IV gastric or lung cancer. We analyzed the coverage spectrum of the human genome in our cfDNA samples. cfDNA exhibited no large regions with significant under-coverage, although we observed unbalanced coverage depth in cfDNA at transcription start sites and exon boundaries as a consequence of biased fragmentation due to ordered nucleosome positioning. We also analyzed the copy number variant status based on the whole-genome sequencing results and found high similarity between copy number profile constructed from tumor samples and cfDNA samples. Overall, we conclude that cfDNA comprises a good representation of the tumor genome in late stage gastric and lung cancer.
authors.affiliation: Geneseeq Technology Inc., Suite 300, MaRS Centre, South Tower, Toronto, Ontario, Canada.
authors.forename: Xiangyuan
authors.identifier: http://orcid.org/0000-0001-7970-0867
authors.initials: X
authors.lastname: Ma
authors.affiliation: Jiangsu Cancer Hospital, 42 Baiziting, Xuanwu, Nanjing, Jiangsu, China.
authors.forename: Liangjun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Geneseeq Technology Inc., Suite 300, MaRS Centre, South Tower, Toronto, Ontario, Canada.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: Geneseeq Technology Inc., Suite 300, MaRS Centre, South Tower, Toronto, Ontario, Canada.
authors.forename: Hua
authors.initials: H
authors.lastname: Bao
authors.affiliation: Nanjing Shihe Jiyin Biotechnology Inc., 17th Floor, Building B, Sino-Danish Life Science Park, 3 Xinjinhu Road, Nanjing, Jiangsu, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanjing Shihe Jiyin Biotechnology Inc., 17th Floor, Building B, Sino-Danish Life Science Park, 3 Xinjinhu Road, Nanjing, Jiangsu, China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Geneseeq Technology Inc., Suite 300, MaRS Centre, South Tower, Toronto, Ontario, Canada.
authors.forename: Yang W
authors.identifier: http://orcid.org/0000-0003-4585-1792
authors.initials: YW
authors.lastname: Shao
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Cang Lang Qu, Suzhou, Jiangsu, China.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D020029:Base Pairing / Q000235:genetics; D002474:Cell-Free System; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D009707:Nucleosomes / Q000235:genetics; D009711:Nucleotides / Q000235:genetics; D025341:Principal Component Analysis; D017422:Sequence Analysis, DNA
chemical_list: D004273:DNA, Neoplasm; D009707:Nucleosomes; D009711:Nucleotides