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Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer.
Stackpole, Mary L; Zeng, Weihua; Li, Shuo; Liu, Chun-Chi; Zhou, Yonggang; He, Shanshan; Yeh, Angela; Wang, Ziye; Sun, Fengzhu; Li, Qingjiao; Yuan, Zuyang; Yildirim, Asli; Chen, Pin-Jung; Winograd, Paul; Tran, Benjamin; Lee, Yi-Te; Li, Paul Shize; Noor, Zorawar; Yokomizo, Megumi; Ahuja, Preeti; Zhu, Yazhen; Tseng, Hsian-Rong; Tomlinson, James S; Garon, Edward; French, Samuel; Magyar, Clara E; Dry, Sarah; Lajonchere, Clara; Geschwind, Daniel; Choi, Gina; Saab, Sammy; Alber, Frank; Wong, Wing Hung; Dubinett, Steven M; Aberle, Denise R; Agopian, Vatche; Han, Steven-Huy B; Ni, Xiaohui; Li, Wenyuan; Zhou, Xianghong Jasmine.
Affiliation
  • Stackpole ML; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Zeng W; EarlyDiagnostics, Inc., 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
  • Li S; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Liu CC; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Zhou Y; EarlyDiagnostics, Inc., 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
  • He S; EarlyDiagnostics, Inc., 570 Westwood Plaza, Los Angeles, CA, 90095, USA.
  • Yeh A; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Wang Z; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Sun F; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Li Q; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Yuan Z; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
  • Yildirim A; The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
  • Chen PJ; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Winograd P; Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Tran B; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Lee YT; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Li PS; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Noor Z; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Yokomizo M; Westlake High School, 100N Lakeview Cyn Road, Westlake Village, CA, 91362, USA.
  • Ahuja P; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Zhu Y; Department of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Tseng HR; Department of Radiological Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Tomlinson JS; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Garon E; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • French S; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Magyar CE; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Dry S; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Lajonchere C; Department of Surgery, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Geschwind D; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Choi G; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Saab S; VA Greater Los Angeles Health Care System, Los Angeles, CA, 90073, USA.
  • Alber F; Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Wong WH; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Dubinett SM; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Aberle DR; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Agopian V; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Han SB; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Ni X; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Li W; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
  • Zhou XJ; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
Nat Commun ; 13(1): 5566, 2022 09 29.
Article in En | MEDLINE | ID: mdl-36175411
ABSTRACT
Early cancer detection by cell-free DNA faces multiple challenges low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Cell-Free Nucleic Acids Type of study: Diagnostic_studies / Health_economic_evaluation / Screening_studies Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Stomach Neoplasms / Cell-Free Nucleic Acids Type of study: Diagnostic_studies / Health_economic_evaluation / Screening_studies Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2022 Document type: Article Affiliation country: Estados Unidos