{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:05:49Z","timestamp":1790255149447,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n The\n KAT6A::NCOA2<\/jats:italic>\n (formerly\n MOZ::TIF2<\/jats:italic>\n ) fusion is an extremely rare recurrent genetic abnormality in acute myeloid leukemia (AML), with only nine cases reported to date. It has consistently been associated with inv(8)(p11q13). However, the genomic mechanism underlying this fusion has remained unresolved. Because both\n KAT6A<\/jats:italic>\n and\n NCOA2<\/jats:italic>\n are transcribed in the same reverse orientation on chromosome 8, a simple inversion is structurally insufficient to generate a transcriptionally competent fusion transcript, creating a long\u2010standing cytogenetic paradox. We analyzed an AML case harboring a\n KAT6A::NCOA2<\/jats:italic>\n fusion using targeted genomic profiling and breakpoint\u2010level validation. In addition to the canonical\n KAT6A::NCOA2<\/jats:italic>\n fusion, sequencing identified an unexpected\n MTFR1::KAT6A<\/jats:italic>\n rearrangement. Since\n MTFR1<\/jats:italic>\n is located between\n KAT6A<\/jats:italic>\n and\n NCOA2<\/jats:italic>\n on chromosome 8, we hypothesized a complex intrachromosomal rearrangement. Genomic breakpoint analysis revealed that the fusion was generated not by a single inv(8), but by two adjacent intrachromosomal inversions forming a tandem double inversion. This rearrangement reoriented genomic segments to place\n KAT6A<\/jats:italic>\n and\n NCOA2<\/jats:italic>\n in a transcriptionally compatible configuration, enabling fusion formation. These findings resolve the structural paradox of\n KAT6A::NCOA2<\/jats:italic>\n \u2010positive AML by demonstrating that a cytogenetically apparent inv(8)(p11q13) can conceal a tandem double\u2010inversion architecture that reorients\n KAT6A<\/jats:italic>\n and\n NCOA2<\/jats:italic>\n into a transcriptionally compatible configuration.\n <\/jats:p>","DOI":"10.1002\/gcc.70171","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:07:16Z","timestamp":1788779236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tandem Double Inversion Resolves the Structural Paradox Underlying Recurrent\n KAT6A::NCOA2<\/i>\n Fusion in Acute Myeloid Leukemia"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8672-5566","authenticated-orcid":false,"given":"Jun","family":"Nagai","sequence":"first","affiliation":[{"name":"Department of Hematology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9998-7147","authenticated-orcid":false,"given":"Shota","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-271X","authenticated-orcid":false,"given":"Takanori","family":"Teshima","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-2864","authenticated-orcid":false,"given":"Masahiro","family":"Onozawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.6.2118"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00587.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009113397"},{"issue":"5","key":"e_1_2_9_5_1","article-title":"A Further Case of Acute Myeloid Leukaemia With Inv(8)(p11q13) and MOZ\u2010TIF2 Fusion","volume":"87","author":"Billio A.","year":"2002","journal-title":"Haematologica"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e318142b547"},{"issue":"4","key":"e_1_2_9_7_1","first-page":"423","article-title":"A Further Case of Acute Myelomonocytic Leukemia With Inv(8) Chromosomal Rearrangement and MOZ\u2010NCOA2 Gene Fusion","volume":"12","author":"Murati A.","year":"2003","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.7193-26"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15427"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8351518"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.10.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.019"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2191"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00457-9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2026.06.004"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg905"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70171","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gcc.70171","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.70171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:35:17Z","timestamp":1790253317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.70171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/gcc.70171"],"URL":"https:\/\/doi.org\/10.1002\/gcc.70171","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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