Optical Genome Mapping in Myelodysplastic Syndromes: Clinical Value and Limitations Derived from a Cohort of 236 Patients.

Identification of cytogenetic abnormalities is critical for the classification and risk stratification of myelodysplastic syndromes (MDS). Optical genome mapping (OGM) is an emerging cytogenomic platform that enables high-resolution genome-wide cytogenetic analysis. We analyzed bone marrow specimens of 236 MDS patients, 149 newly diagnosed and 87 with relapsed/refractory disease, using OGM, conventional karyotyping and next-generation sequencing analysis. OGM and karyotyping showed concordant results in 68% of cases, including 34% with normal findings by both assays. OGM provided additional information in 27% of patients. Common abnormalities detected exclusively by OGM included chromoanagenesis (n=33), KMT2A partial tandem duplication (n=7) and MECOM rearrangement (n=4). These OGM findings led to disease reclassification and/or changes in risk stratification in 14 (9.4%) patients with newly diagnosed MDS. On the other hand, OGM failed to detect small clones or subclones in 5% patients, resulting in risk group changes in 2% of newly diagnosed MDS patients. We conclude that OGM enhances the cytogenetic assessment of MDS in approximately 25% of patients and leads to a change in disease classification and/or risk stratification in ∼10% of patients. However, low sensitivity for detecting small clones or subclones remains a limitation of OGM.