Technical and Clinical Validation of Optical Genome Mapping

Technical and clinical validation of optical genome mapping @RadboudUMC Kornelia Neveling,1,2 Tuomo Mantere,1,3,4 Susan Vermeulen,1 Michiel Oorsprong,1 Ronald van Beek,1 Ellen Kater-Baats,1 Marc Pauper,1 Guillaume van der Zande,1 Dominique Smeets,1 Su Ming Sun,5 Brigitte Verbeek,5 Simone Wezenberg,1 Stijn Ghesquiere,5 Lisenka Vissers,1 Daniel Olde Weghuis,1 Marian JPL Stevens-Kroef,1 Alexander Hoischen1,3,6 1Department of Human Genetics, Radboud university medical center, Nijmegen, 6500 HB, The Netherlands, 2Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands, 3Radboud Institute of Medical Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands, 4Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, Oulu, Finland, 5Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands, 6Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6532 GA Nijmegen, The Netherlands. Somatic structural variants (SVs) are important drivers of cancer development and progression, and are relevant for the prognosis and a determinant in treatment decision making. In a diagnostic set-up, especially for hematological malignancies, the comprehensive SV analysis still requires a combination of cytogenetic techniques (karyotyping, FISH, CNV-microarrays). We hypothesize that the combination of these classical approaches could be replaced by optical genome mapping (OGM). To investigate this hypothesis, samples from 52 patients with a clinical diagnosis of a hematological malignancy and an abnormal cytogenetic result were analyzed as part of a retrospective technical validation study. Detailed technical comparison with standard-of-care tests showed high analytical validity of OGM, resulting in a sensitivity of 100%, with a positive predictive value.