{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:04:04Z","timestamp":1780578244800,"version":"3.54.1"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Chromosomal microarray analysis (CMA) is an essential tool in modern cytogenetics for detecting copy number alterations and copy-neutral loss of heterozygosity (CN-LOH). As optical genome mapping (OGM) emerges as a potential replacement for traditional cytogenetic methods, the extent to which CMA remains necessary in routine diagnostic workflows remains to be elucidated. Methods: We retrospectively reviewed 53 primary neoplastic cases, selected from a larger cohort of 327 hematologic malignancy specimens, in which CMA identified one or more CN-LOH events. Event size, genomic content, and correlation with next-generation sequencing (NGS) findings were assessed. A separate cohort of newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) was analyzed to evaluate disease-specific CN-LOH frequency. Results: Nearly half of CN-LOH events detected were &lt;25 Mb, below the current detection threshold of OGM inferred from published benchmarks and validated workflows. Many encompassed clinically relevant genes, including FLT3, JAK2, TET2, TP53, and RUNX1. Additionally, two-thirds of cases harbored pathogenic or likely pathogenic variants by NGS within the corresponding CN-LOH regions, further underscoring the clinical value of detecting these copy-neutral events. In contrast, CN-LOH was uncommon in B-ALL, and most alterations identified by CMA would be detectable by OGM. Many of these patients also harbored complex structural rearrangements that required multiple conventional assays for full characterization; these could be resolved by OGM in a single analysis. Conclusions: Our findings indicate that although OGM excels at resolving complex structural variants, CMA remains essential for detecting copy-neutral events. Until OGM achieves improved sensitivity for CN-LOH, an integrated approach utilizing conventional cytogenetics, CMA, NGS, and OGM provides the most reliable framework for comprehensive genomic assessment across cancer types.<\/jats:p>","DOI":"10.3390\/cancers18111841","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:52:30Z","timestamp":1780573950000},"page":"1841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SNP-Based Chromosomal Microarray Analysis in the Era of Optical Genome Mapping: An Enriched Case-Series Evaluating Copy-Neutral Events"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1448-7353","authenticated-orcid":false,"given":"Alexander R.","family":"Marr","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1594-0233","authenticated-orcid":false,"given":"Patrick R.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Golem","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gersen, S.L., and Keagle, M.B. 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