title: Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients.
abstract: The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z-score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: Peiyong
authors: P
authors: Jiang
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: Carol W M
authors: CW
authors: Chan
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: K C Allen
authors: KC
authors: Chan
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: Suk Hang
authors: SH
authors: Cheng
authors: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: John
authors: J
authors: Wong
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; Institute of Digestive Diseases, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; and.
authors: Vincent Wai-Sun
authors: VW
authors: Wong
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; Institute of Digestive Diseases, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; and.
authors: Grace L H
authors: GL
authors: Wong
authors: State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
authors: Stephen L
authors: SL
authors: Chan
authors: State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
authors: Tony S K
authors: TS
authors: Mok
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; Institute of Digestive Diseases, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; and.
authors: Henry L Y
authors: HL
authors: Chan
authors: State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: Paul B S
authors: PB
authors: Lai
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong;
authors: Rossa W K
authors: RW
authors: Chiu
authors: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong; Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; loym@cuhk.edu.hk.
authors: Y M Dennis
authors: YM
authors: Lo
mesh_terms: D020029:Base Pairing / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004272:DNA, Mitochondrial / Q000097:blood; D004273:DNA, Neoplasm / Q000097:blood*; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics; D008970:Molecular Weight; D012372:ROC Curve
chemical_list: D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm
keywords: circulating tumor DNA; liquid biopsy; massively parallel sequencing; mitochondrial DNA; tumor markers
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