{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:02:42Z","timestamp":1780570962338,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007919","name":"University of Massachusetts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007919","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"Aims<\/jats:title>Genes affecting epigenetic pathways are frequently mutated in myeloid malignancies, including acute myeloid leukaemia (AML<\/jats:styled-content>). The genes encoding TET<\/jats:styled-content>2<\/jats:italic>, IDH<\/jats:styled-content>1<\/jats:italic> and IDH<\/jats:styled-content>2<\/jats:italic> are among the most commonly mutated genes, and cause defective conversion of 5\u2010methylcytosine into 5\u2010hydroxymethylcytosine (5hmC), impairing demethylation of DNA<\/jats:styled-content>, and presumably serving as driver mutations in leukaemogenesis. The aim of this study was to correlate 5hmC immunohistochemical loss with the mutation status of genes involved in epigenetic pathways in AML<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods and results<\/jats:title>Immunohistochemical staining with an anti\u20105hmC antibody was performed on 41 decalcified, formalin\u2010fixed paraffin\u2010embedded (FFPE<\/jats:styled-content>) bone marrow biopsies from patients with AML<\/jats:styled-content>. Archived DNA<\/jats:styled-content> was subjected to next\u2010generation sequencing for analysis of a panel of genes, including TET<\/jats:styled-content>2<\/jats:italic>, IDH<\/jats:styled-content>1<\/jats:italic>, IDH<\/jats:styled-content>2<\/jats:italic>, WT<\/jats:styled-content>1<\/jats:italic> and DNMT<\/jats:styled-content>3A<\/jats:italic>. TET<\/jats:styled-content>2<\/jats:italic>, IDH<\/jats:styled-content>1<\/jats:italic>, IDH<\/jats:styled-content>2<\/jats:italic>, WT<\/jats:styled-content>1<\/jats:italic> and DNMT<\/jats:styled-content>3A<\/jats:italic> mutations were found in 46% (19\/41) of the cases. Ten of 15 cases (67%) with TET<\/jats:styled-content>2<\/jats:italic>, IDH<\/jats:styled-content>1<\/jats:italic>, IDH<\/jats:styled-content>2<\/jats:italic> or WT<\/jats:styled-content>1<\/jats:italic> mutations showed deficient 5hmC staining, whereas nine of 26 cases (35%) without a mutation in these genes showed loss of 5hmC. It is of note that all four cases with TET<\/jats:styled-content>2<\/jats:italic> mutations showed deficient 5hmC staining.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Overall, somatic mutations in TET<\/jats:styled-content>2<\/jats:italic>, IDH<\/jats:styled-content>1<\/jats:italic>, IDH<\/jats:styled-content>2<\/jats:italic>, WT<\/jats:styled-content>1<\/jats:italic> and DNMT<\/jats:styled-content>3A<\/jats:italic> were common in our cohort of AML<\/jats:styled-content> cases. Immunohistochemical staining for 5hmC was lost in the majority of cases harbouring mutations in these genes, reflecting the proposed relationship between dysfunctional epigenetic pathways and leukaemogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13046","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T13:51:23Z","timestamp":1469541083000},"page":"1055-1065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunohistochemical loss of 5\u2010hydroxymethylcytosine expression in acute myeloid leukaemia: relationship to somatic gene mutations affecting epigenetic pathways"],"prefix":"10.1111","volume":"69","author":[{"given":"Minoti","family":"Magotra","sequence":"first","affiliation":[{"name":"Department of Pathology University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School Worcester MA 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Pathology University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd M","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A","family":"Woda","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School Worcester MA 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