Utilizing nullomers in cell-free RNA for early cancer detection.

Autor: Montgomery A; Institute for Personalized Medicine, Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Tsiatsianis GC; Institute for Personalized Medicine, Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.; School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece., Mouratidis I; Institute for Personalized Medicine, Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, USA., Chan CSY; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA., Athanasiou M; School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece., Papanastasiou AD; Department of Biomedical Sciences, University of West Attica, Athens, Greece., Kantere V; School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece., Syrigos N; Third Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., Vathiotis I; Third Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., Syrigos K; Third Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., Yee NS; Next Generation Therapies Program, Penn State Cancer Institute; Division of Hematology-Oncology, Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA., Georgakopoulos-Soares I; Institute for Personalized Medicine, Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, USA. izg5139@psu.edu.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2024 Jun; Vol. 31 (6), pp. 861-870. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1038/s41417-024-00741-3
Abstrakt: Early detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome. We also identify nullomer emerging mutational hotspots within tumor genes. Finally, we provide evidence for the identification of nullomers in cell-free RNA from peripheral blood samples, enabling detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: