BACKGROUND: Cell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis, and monitoring. We hypothesized that mining the patterns of cfDNA shallow whole-genome sequencing datasets from patients with cancer could improve cancer detection. METHODS: By applying unsupervised clustering and supervised machine learning on large cfDNA shallow whole-genome sequencing datasets from healthy individuals (n = 367) and patients with different hematological (n = 238) and solid malignancies (n = 320), we identified cfDNA signatures that enabled cancer detection and typing. RESULTS: Unsupervised clustering revealed cancer type-specific sub-grouping. Classification using a supervised machine learning model yielded accuracies of 96% and 65% in discriminating hematological and solid malignancies from healthy controls, respectively. The accuracy of disease type prediction was 85% and 70% for the hematological and solid cancers, respectively. The potential utility of managing a specific cancer was demonstrated by classifying benign from invasive and borderline adnexal masses with an area under the curve of 0.87 and 0.74, respectively. CONCLUSIONS: This approach provides a generic analytical strategy for non-invasive pan-cancer detection and cancer type prediction.

Centre for Human Genetics University Hospitals Leuven Leuven Belgium

Department of Chronic Diseases and Metabolism Laboratory of Respiratory Diseases and Thoracic Surgery KU Leuven Leuven Belgium

Department of Development and Regeneration Woman and Child KU Leuven Leuven Belgium

Department of General Medical Oncology Leuven Cancer Institute University Hospitals Leuven Leuven Belgium

Department of Gynecology and Obstetrics University Hospitals Leuven Leuven Belgium

Department of Hematology University Hospitals Leuven Leuven Belgium

Department of Human Genetics Laboratory for Cytogenetics and Genome Research KU Leuven Leuven Belgium

Department of Human Genetics Laboratory of Genetics of Malignant Diseases KU Leuven Leuven Belgium

Department of Human Genetics Laboratory of Translational Genetics VIB KU Leuven Leuven Belgium

Department of Obstetrics and Gynaecology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Oncology Laboratory of Experimental Oncology KU Leuven Leuven Belgium

Department of Oncology Laboratory of Gynecological Oncology KU Leuven Leuven Belgium

Department of Oncology Laboratory of Tumor Immunology and Immunotherapy Leuven Cancer Institute KU Leuven Leuven Belgium

Department of Oncology Molecular Digestive Oncology KU Leuven Leuven Belgium

Department of Pneumology University Hospitals Leuven Leuven Belgium

Department of Surgery Center for Gynecological Oncology Amsterdam Academic Medical Centre Amsterdam University of Amsterdam and the Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam the Netherlands

Department of Woman and Child Health Fondazione Policlinico Universitario A Gemelli IRCCS Università Cattolica del Sacro Cuore Roma Rome Italy

Multidisciplinary Breast Centre Leuven Cancer Institute University Hospitals Leuven Leuven Belgium

Citace poskytuje Crossref.org