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      Circulating Tumor DNA as Biomarkers for Cancer Detection

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          Abstract

          Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important component of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are currently underway, clinical translation of ctDNA detection in various types of cancers has been attracting much attention, due to the great potential of ctDNA as blood-based biomarkers for early diagnosis and treatment of cancers. ctDNAs are detected and tracked primarily based on tumor-related genetic and epigenetic alterations. In this article, we reviewed the available studies on ctDNA detection and described the representative methods. We also discussed the current understanding of ctDNAs in cancer patients and their availability as potential biomarkers for clinical purposes. Considering the progress made and challenges involved in accurate detection of specific cell-free nucleic acids, ctDNAs hold promise to serve as biomarkers for cancer patients, and further validation is needed prior to their broad clinical use.

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          Most cited references119

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          Detection, clinical relevance and specific biological properties of disseminating tumour cells.

          Most cancer deaths are caused by haematogenous metastatic spread and subsequent growth of tumour cells at distant organs. Disseminating tumour cells present in the peripheral blood and bone marrow can now be detected and characterized at the single-cell level. These cells are highly relevant to the study of the biology of early metastatic spread and provide a diagnostic source in patients with overt metastases. Here we review the evidence that disseminating tumour cells have a variety of uses for understanding tumour biology and improving cancer treatment.
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            Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients.

            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.
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              Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer.

              Early indicators of treatment response in metastatic colorectal cancer (mCRC) could conceivably be used to optimize treatment. We explored early changes in circulating tumor DNA (ctDNA) levels as a marker of therapeutic efficacy.
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                Author and article information

                Contributors
                Journal
                Genomics Proteomics Bioinformatics
                Genomics Proteomics Bioinformatics
                Genomics, Proteomics & Bioinformatics
                Elsevier
                1672-0229
                2210-3244
                07 April 2017
                April 2017
                07 April 2017
                : 15
                : 2
                : 59-72
                Affiliations
                [1 ]CAS Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
                [2 ]University of Chinese Academy of Sciences, Beijing 100049, China
                Author notes
                [* ]Corresponding author. sunyl@ 123456big.ac.cn
                [a]

                ORCID: 0000-0001-9262-7254.

                [b]

                ORCID: 0000-0003-0573-7856.

                [c]

                ORCID: 0000-0002-8401-5554.

                Article
                S1672-0229(17)30048-7
                10.1016/j.gpb.2016.12.004
                5414889
                28392479
                e6625a89-b4ef-4674-9c41-e890614ad5cb
                © 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 1 July 2016
                : 13 December 2016
                : 20 December 2016
                Categories
                Review

                precision medicine,liquid biopsy,circulating tumor dna,biomarker,clinical diagnosis,cell-free nucleic acids

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