{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:15:27Z","timestamp":1791918927717,"version":"4.3.4"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Chromosomal structural variations (SVs) play an important role in the formation of human cancers, including leukemias. However, many complex SVs cannot be identified by conventional tools, including karyotyping, fluorescence <jats:italic>in situ<\/jats:italic> hybridization, microarrays, and multiplex ligation-dependent probe amplification (MLPA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Optical genome mapping (OGM) and whole genome sequencing (WGS) were employed to analyze five leukemia samples with SVs detected by karyotyping, MLPA, and RNA sequencing (RNA-seq). OGM was performed using the Saphyr chip on a Bionano Saphyr system. Copy number variation and rare variant assembly analyses were performed with Bionano software v3.7. WGS was analyzed by the Manta program for SVs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The leukemia samples had an average of 477 insertions, 457 deletions, and 32 inversions, which were significantly greater than those of the normal blood samples (<jats:italic>p<\/jats:italic> = 0.016, 0.028, and 0.028, respectively). In <jats:xref>Case 1<\/jats:xref>, OGM detected a sequential translocation between chromosomes 5, 8, 12, and 21 and <jats:italic>ETV6::RUNX1<\/jats:italic> and <jats:italic>BCAT1::BAALC<\/jats:italic> gene fusions. <jats:xref>Case 2<\/jats:xref> had two pathogenic SVs and a <jats:italic>BCR::ABL1<\/jats:italic> fusion. <jats:xref>Case 3<\/jats:xref> had one pathogenic SV and an <jats:italic>IGH::DUSP22<\/jats:italic> fusion. <jats:xref>Case 4<\/jats:xref> had two pathogenic SVs and a <jats:italic>CBFB::MYH11<\/jats:italic> fusion. <jats:xref>Case 5<\/jats:xref> had an <jats:italic>STIL::TAL1<\/jats:italic> fusion. All breakpoint sequences were defined by WGS. An <jats:italic>IGH::DUX4<\/jats:italic> fusion previously found by RNA-seq in <jats:xref>Case 3<\/jats:xref> was not confirmed because <jats:italic>DUX4<\/jats:italic>, which has multiple pseudogenes, was refractory to OGM and WGS analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>OGM is a fundamental tool that complements G-banding analysis in identifying complex SVs in leukemia samples, and WGS effectively closes the gaps in OGM mapping.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1496847","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T06:47:49Z","timestamp":1743576469000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Optical genome mapping with whole genome sequencing identifies complex chromosomal structural variations in acute leukemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Meng-Ju Melody","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Jung","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Huei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Hsiu","family":"Chien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuh-Liang","family":"Hwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui-Yan","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni-Chung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Li","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1080\/14796694.2024.2385296","article-title":"Cancer cytogenetics in the era of artificial intelligence: shaping the future of chromosome analysis","volume":"20","author":"Alain","year":"2024","journal-title":"Future Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1038\/leu.2016.383","article-title":"Mutations in NOTCH1 PEST domain orchestrate CCL19-driven homing of chronic lymphocytic leukemia cells by modulating the tumor suppressor gene DUSP22","volume":"31","author":"Arruga","year":"2017","journal-title":"Leukemia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1684\/abc.2016.1176","article-title":"Cytogenetics in the management of children and adult acute lymphoblastic leukemia (ALL): an update by the Groupe francophone de cytog\u00e9n\u00e9tique h\u00e9matologique (GFCH)","volume":"74","author":"Baranger","year":"2016","journal-title":"Ann. 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