{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:39:46Z","timestamp":1790739586020,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Foundation de Drie Lichten, Leiden, The Netherlands"},{"name":"The Rene Vogels Foundation"},{"name":"JSM-Ubbo Emmius Foundation Talent Grant"},{"name":"German Ministry for Education and Science","award":["0316166"],"award-info":[{"award-number":["0316166"]}]},{"name":"German Ministry for Education and Science","award":["031A428H"],"award-info":[{"award-number":["031A428H"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Aims<\/jats:title>Low\u2010grade follicular lymphoma (FL<\/jats:styled-content>) (grade 1\/2, FL<\/jats:styled-content>1\/2) has an annual risk of transformation of \u22483%, which is associated with aberrations in CDKN<\/jats:styled-content>2A<\/jats:italic>\/B<\/jats:italic>, TP<\/jats:styled-content>53<\/jats:italic>, and MYC<\/jats:styled-content><\/jats:italic>. As in diffuse large B\u2010cell lymphoma, high MYC<\/jats:styled-content> expression in transformed FL<\/jats:styled-content> (tFL<\/jats:styled-content>) might predict a MYC<\/jats:styled-content><\/jats:italic> breakpoint.<\/jats:p><\/jats:sec>Methods and results<\/jats:title>We quantified MYC<\/jats:styled-content> expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL<\/jats:styled-content>1\/2 with subsequent transformation and in four isolated biopsies of tFL<\/jats:styled-content>. As controls, 28 biopsies of FL<\/jats:styled-content>1\/2 without transformation (median follow\u2010up of 105 months) and nine biopsies of FL<\/jats:styled-content>3A\/B were analysed. In the 20 FL<\/jats:styled-content>1\/2\u2013tFL<\/jats:styled-content> pairs, MYC<\/jats:styled-content> expression was significantly higher in tFL<\/jats:styled-content> than in the initial FL<\/jats:styled-content>1\/2 biopsies (median 54% versus 6%; 7% in FL<\/jats:styled-content>3A, and 35% in FL<\/jats:styled-content>3B). MYC<\/jats:styled-content><\/jats:italic> breaks (MYC<\/jats:styled-content><\/jats:italic>\u2010R) were detected in eight of 21 (38%) tFL<\/jats:styled-content>s analysed by fluorescence in\u2010situ<\/jats:italic> hybridization (FISH<\/jats:styled-content>), with a median MYC<\/jats:styled-content> score of 86%. In two of the analysed tFL<\/jats:styled-content> cases, the translocation was already detected in antecedent FL<\/jats:styled-content>1\/2. MYC<\/jats:styled-content><\/jats:italic> partners were immunoglobulin (IG<\/jats:styled-content>) loci in three of eight cases (one IGL<\/jats:styled-content>, one IGH<\/jats:styled-content>, and one IGK<\/jats:styled-content>) and non\u2010IG<\/jats:styled-content> in five of eight cases (two PAX<\/jats:styled-content>5<\/jats:italic>, one BCL6<\/jats:italic>, and two unknown). Of the eight MYC<\/jats:styled-content><\/jats:italic>\u2010R+ cases, six were BCL2<\/jats:italic>+\/MYC<\/jats:styled-content><\/jats:italic>+ double\u2010hit, one was BCL2<\/jats:italic>+\/BCL6<\/jats:italic>+\/MYC<\/jats:styled-content><\/jats:italic>+ triple\u2010hit, and one was MYC<\/jats:styled-content><\/jats:italic>+ single\u2010hit. All three IG<\/jats:styled-content><\/jats:italic>\u2010MYC<\/jats:styled-content><\/jats:italic>+ cases showed a MYC<\/jats:styled-content> expression level of >85%, whereas the five cases with a non\u2010IG <\/jats:styled-content>MYC<\/jats:styled-content><\/jats:italic> partner had a wider range of expression (median 68%, range 13\u201386%). Among the 13 MYC<\/jats:styled-content><\/jats:italic>\u2010R\u2212 tFL<\/jats:styled-content>s, two groups with almost dichotomous MYC<\/jats:styled-content> expression could be observed (three cases showed \u226590% MYC<\/jats:styled-content> expression), suggesting alternative mechanisms of MYC<\/jats:styled-content> activation.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>we show an increase in MYC<\/jats:styled-content> expression from FL<\/jats:styled-content>1\/2 to tFL<\/jats:styled-content>. MYC<\/jats:styled-content><\/jats:italic> breakpoints were present in \u224840% of the cases, which is markedly higher than in de novo <\/jats:italic>DLBCL<\/jats:styled-content>. MYC<\/jats:styled-content> expression was uniformly high in cases with an IG<\/jats:styled-content>\u2010MYC<\/jats:styled-content><\/jats:italic> translocation but much more heterogeneous and in part independent of the presence of a MYC<\/jats:styled-content><\/jats:italic> break in non\u2010IG<\/jats:styled-content>\u2010MYC<\/jats:styled-content><\/jats:italic> and MYC<\/jats:styled-content><\/jats:italic>\u2010negative cases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13316","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T08:36:22Z","timestamp":1500626182000},"page":"960-971","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["MYC<\/scp> expression and translocation analyses in low\u2010grade and transformed follicular lymphoma"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-0320","authenticated-orcid":false,"given":"Sietse M","family":"Aukema","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Hospital Schleswig\u2010Holstein Campus Kiel\/Christian Albrechts University Kiel Kiel Germany"},{"name":"Department of Pathology & Medical Biology University of Groningen University Medical Centre Groningen Groningen The Netherlands"},{"name":"Institute of Pathology Division of Haematopathology University Medical Centre Schleswig\u2010Holstein Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"van Pel","sequence":"additional","affiliation":[{"name":"Department of Pathology & Medical Biology University of Groningen University Medical Centre Groningen Groningen The Netherlands"},{"name":"Department of Haematology University of Groningen University Medical Centre Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Nagel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Schleswig\u2010Holstein Campus Kiel\/Christian Albrechts University Kiel Kiel Germany"},{"name":"Institute of Experimental and Clinical Pharmacology University Hospital Schleswig\u2010Holstein, Campus Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Bens","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Schleswig\u2010Holstein Campus Kiel\/Christian Albrechts University Kiel Kiel Germany"},{"name":"Institute of Human Genetics University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Siebert","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Schleswig\u2010Holstein Campus Kiel\/Christian Albrechts University Kiel Kiel Germany"},{"name":"Institute of Human Genetics University of Ulm Ulm 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