{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:18:46Z","timestamp":1792001926876,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006364","name":"Institut National Du Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>T\u2010lymphoblastic lymphoma (T\u2010LBL) and thymoma are two rare primary tumors of the thymus deriving either from T\u2010cell precursors or from thymic epithelial cells, respectively. Some thymoma subtypes (AB, B1, and B2) display numerous reactive terminal deoxynucleotidyl transferase\u2010positive (TdT<jats:sup>+<\/jats:sup>) T\u2010cell precursors masking epithelial tumor cells. Therefore, the differential diagnosis between T\u2010LBL and TdT<jats:sup>+<\/jats:sup> T\u2010lymphocyte\u2010rich thymoma could be challenging, especially in the case of needle biopsy. To distinguish between T\u2010LBL and thymoma\u2010associated lymphoid proliferations, we analyzed the global DNA methylation using two different technologies, namely MeDIP array and EPIC array, in independent samples series [17 T\u2010LBLs compared with one TdT<jats:sup>+<\/jats:sup> lymphocyte\u2010rich thymoma (B1 subtype) and three normal thymi, and seven lymphocyte\u2010rich thymomas compared with 24 T\u2010LBLs, respectively]. In unsupervised principal component analysis (PCA), T\u2010LBL and thymoma samples clustered separately. We identified differentially methylated regions (DMRs) using MeDIP\u2010array and EPIC\u2010array datasets and nine overlapping genes between the two datasets considering the top 100 DMRs including <jats:italic>ZIC1<\/jats:italic>, <jats:italic>TSHZ2<\/jats:italic>, <jats:italic>CDC42BPB<\/jats:italic>, <jats:italic>RBM24<\/jats:italic>, <jats:italic>C10orf53<\/jats:italic>, and <jats:italic>MACROD<\/jats:italic>2. In order to explore the DNA methylation profiles in larger series, we defined a classifier based on these six differentially methylated gene promoters, developed an MS\u2010MLPA assay, and demonstrated a significant differential methylation between thymomas (hypomethylated; <jats:italic>n<\/jats:italic>\u2009=\u200948) and T\u2010LBLs (hypermethylated; <jats:italic>n<\/jats:italic>\u2009=\u200954) (methylation ratio median 0.03 versus 0.66, respectively; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), with <jats:italic>MACROD2<\/jats:italic> methylation status the most discriminating. Using a machine learning strategy, we built a prediction model trained with the EPIC\u2010array dataset and defined a cumulative score taking into account the weight of each feature. A score above or equal to 0.4 was predictive of T\u2010LBL and conversely. Applied to the MS\u2010MLPA dataset, this prediction model accurately predicted diagnoses of T\u2010LBL and thymoma. \u00a9 2024 The Author(s). <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6346","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T08:08:19Z","timestamp":1727424499000},"page":"284-292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>DNA<\/scp> methylation as a new tool for the differential diagnosis between T\u2010<scp>LBL<\/scp> and lymphocyte\u2010rich thymoma"],"prefix":"10.1002","volume":"264","author":[{"given":"Mehdi","family":"Latiri","sequence":"first","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Belhocine","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille University, INSERM, TAGC, UMR1090, Equipe Lab\u00e9lis\u00e9e Ligue Contre le Cancer  Marseille France"},{"name":"Department of Molecular Medicine,Al\u2010Jawhara Centre for Molecular Medicine,Genetics, and Inherited Disorders Arabian Gulf University  Manama Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Smith","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Garnier","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Hematology and Oncology Hospices Civils de Lyon, Claude Bernard Lyon 1 University  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Balducci","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Pinton","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume P","family":"Andrieu","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Department of Pathology H\u00f4pital Necker\u2010Enfants Malades, Universit\u00e9 Paris\u2013Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Spicuglia","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille University, INSERM, TAGC, UMR1090, Equipe Lab\u00e9lis\u00e9e Ligue Contre le Cancer  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Jamain","sequence":"additional","affiliation":[{"name":"Univ Paris Est Cr\u00e9teil, INSERM, IMRB, Translational Neuropsychiatry  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-9121","authenticated-orcid":false,"given":"Violaine","family":"Latapie","sequence":"additional","affiliation":[{"name":"Univ Paris Est Cr\u00e9teil, INSERM, IMRB, Translational Neuropsychiatry  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent Thomas","family":"de Montpreville","sequence":"additional","affiliation":[{"name":"Department of Pathology Marie\u2010Lannelongue Hospital  Le Plessis\u2010Robinson France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Chalabreysse","sequence":"additional","affiliation":[{"name":"Department of Pathology Groupe Hospitalier Est, Hospices Civils de Lyon  Bron France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Marx","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girard","sequence":"additional","affiliation":[{"name":"Thorax Institute Curie Montsouris  Paris France"},{"name":"Universite de Versailles Saint Quentin (UVSQ), Paris\u2013Saclay University  Versailles France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Besse","sequence":"additional","affiliation":[{"name":"Department of Cancer Medicine Gustave Roussy Cancer Campus  Villejuif France"},{"name":"Paris\u2013Saclay University  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Plass","sequence":"additional","affiliation":[{"name":"German Cancer Research Center Division of Cancer Epigenomics  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Gibault","sequence":"additional","affiliation":[{"name":"Department of Pathology HEGP Hospital  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Badoual","sequence":"additional","affiliation":[{"name":"Department of Pathology HEGP Hospital  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Macintyre","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Asnafi","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry Jo","family":"Molina","sequence":"additional","affiliation":[{"name":"Department of Pathology H\u00f4pital Necker\u2010Enfants Malades, Universit\u00e9 Paris\u2013Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-2292","authenticated-orcid":false,"given":"Aurore","family":"Touzart","sequence":"additional","affiliation":[{"name":"Laboratory of Onco\u2010Hematology Necker Children's Hospital, Assistance Publique\u2010H\u00f4pitaux de Paris (AP\u2010HP)  Paris France"},{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, INSERM U1151, Institut Necker Enfants Malades (INEM)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.10.010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-014-1606-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2018-205399"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.11.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227197"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv277"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.5385"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.7661"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.11.011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2115-8_3"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000255"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403202"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-409"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.223677"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc4834"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqv024"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-022-01063-1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000095"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1844"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcab042"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12926"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1083"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-020-00958-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2020.100559"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2019-0331"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901372RR"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13066"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-1971-4"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3566"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abe6156"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.52109"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/1176934320954868"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2021.12935"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.252"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.383"},{"key":"e_1_2_8_37_1","first-page":"465","article-title":"Identification of novel functional variants of SIN3A and SRSF1 among somatic variants in acute myeloid leukemia patients","volume":"41","author":"Min J\u2010W","year":"2018","journal-title":"Mol Cells"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2015.03.012"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-020-0122-7"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25887"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0338"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2015.06.005"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.6346","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:33:18Z","timestamp":1761039198000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.6346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/path.6346"],"URL":"https:\/\/doi.org\/10.1002\/path.6346","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"2023-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}