{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:57:25Z","timestamp":1763751445117,"version":"3.45.0"},"reference-count":51,"publisher":"BMJ","issue":"7","funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101112687","724281"],"award-info":[{"award-number":["101112687","724281"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09120012010023","12949","14726"],"award-info":[{"award-number":["09120012010023","12949","14726"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Radboud Oncology Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Louise Vehmeijer Stichting","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Institute of Chemical Immunology","award":["ICI 000-23"],"award-info":[{"award-number":["ICI 000-23"]}]},{"name":"Netherlands Organization for Scientific Research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2025,1,6]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Follicular lymphoma (FL) is characterised by significant heterogeneity in both the clinical trajectories and the molecular profiles. This study aimed to investigate clonal dynamics in FL by analysing mutation profiles at various time points during the disease course including at histological transformation (HT), to gain insight into the mutational changes over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analysed 76 biopsies from 25 patients, including 13 cases with three or more FL biopsies and 12 cases with subsequent HT. Hybrid capture-based Next-Generation Sequencing (NGS) with the EuroClonality-NGS DNA capture (EuroClonality-NDC) assay was used to examine clonal rearrangements and mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 204 (potentially) pathogenic mutations were identified. Only 40% of mutations remained stably present during a median follow-up period of 139 months (range 9\u2013198).\n                      <jats:italic>KMT2D<\/jats:italic>\n                      and\n                      <jats:italic>CREBBP<\/jats:italic>\n                      were the most frequently mutated genes at diagnosis, exhibiting relative stability in follow-up biopsies. Conversely,\n                      <jats:italic>EZH2<\/jats:italic>\n                      displayed a dynamic pattern of mutations gained and lost during the disease course. At HT, pathogenic mutations affecting\n                      <jats:italic>B2M<\/jats:italic>\n                      ,\n                      <jats:italic>MYC<\/jats:italic>\n                      and\n                      <jats:italic>TP53<\/jats:italic>\n                      emerged. Changes in mutational burden were observed in both FL-sequential and diagnosis-transformation cohorts, with more pronounced changes in the latter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This real-world study provides insights into the complex molecular pathogenesis of FL and HT. As targeted therapies emerge as treatment modalities, mutational profiles could influence treatment decisions in the future. Therefore, recognising the significant changes occurring in the mutational landscape of FL throughout the disease course is crucial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2024-209880","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T13:20:35Z","timestamp":1738329635000},"page":"473-482","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Mutational profile dynamics in follicular lymphoma and large cell transformation"],"prefix":"10.1136","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0319-7505","authenticated-orcid":false,"given":"Eva A M","family":"Hesius","sequence":"first","affiliation":[{"name":"Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy B C","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P","family":"Stewart","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie I","family":"Kroeze","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen van der","family":"Spek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rijnstate Hospital, Arnhem, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djamila","family":"Issa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peet","family":"Nooijen","sequence":"additional","affiliation":[{"name":"Pathology-DNA, Jeroen Bosch Hospital, 's-Hertogenbosch, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen","family":"Luijks","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia J T A","family":"Groenen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M A","family":"Blijlevens","sequence":"additional","affiliation":[{"name":"Department of Hematology, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemiek B van","family":"Spriel","sequence":"additional","affiliation":[{"name":"Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiel van den","family":"Brand","sequence":"additional","affiliation":[{"name":"Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands"},{"name":"Pathology-DNA, Rijnstate Hospital, Arnhem, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"2025112110485703000_78.7.473.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-01048-6"},{"key":"2025112110485703000_78.7.473.2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13316"},{"key":"2025112110485703000_78.7.473.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.3990"},{"key":"2025112110485703000_78.7.473.4","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0111"},{"key":"2025112110485703000_78.7.473.5","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.175"},{"key":"2025112110485703000_78.7.473.6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-457283"},{"key":"2025112110485703000_78.7.473.7","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2856"},{"key":"2025112110485703000_78.7.473.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00169-2"},{"key":"2025112110485703000_78.7.473.9","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.80401"},{"key":"2025112110485703000_78.7.473.10","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.094474"},{"key":"2025112110485703000_78.7.473.11","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000579","article-title":"The Premalignant Ancestor Cell of t(14;18)+ Lymphoma","volume":"5","author":"Brisou","year":"2021","journal-title":"HemaSphere"},{"key":"2025112110485703000_78.7.473.12","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021005284"},{"key":"2025112110485703000_78.7.473.13","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0208"},{"key":"2025112110485703000_78.7.473.14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-717355"},{"key":"2025112110485703000_78.7.473.15","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010779"},{"key":"2025112110485703000_78.7.473.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0043-y"},{"key":"2025112110485703000_78.7.473.17","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16159"},{"key":"2025112110485703000_78.7.473.18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-07-865428"},{"key":"2025112110485703000_78.7.473.19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-272278"},{"key":"2025112110485703000_78.7.473.20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002197","article-title":"Histological Transformation and Progression in Follicular Lymphoma: A Clonal Evolution Study","volume":"13","author":"Kridel","year":"2016","journal-title":"PLoS Med"},{"key":"2025112110485703000_78.7.473.21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0212813","article-title":"Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma","volume":"14","author":"Gonz\u00e1lez-Rinc\u00f3n","year":"2019","journal-title":"PLoS One"},{"key":"2025112110485703000_78.7.473.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.12.027"},{"key":"2025112110485703000_78.7.473.23","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.209"},{"key":"2025112110485703000_78.7.473.24","doi-asserted-by":"publisher","DOI":"10.1002\/path.6235"},{"key":"2025112110485703000_78.7.473.25","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.254854"},{"key":"2025112110485703000_78.7.473.26","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-024-01124-5","article-title":"Multi-omics profiling of longitudinal samples reveals early genomic changes in follicular lymphoma","volume":"14","author":"Bai","year":"2024","journal-title":"Blood Cancer J"},{"key":"2025112110485703000_78.7.473.27","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.23014"},{"key":"2025112110485703000_78.7.473.28","unstructured":"Swerdlow SH , CE H . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edn. 2017."},{"key":"2025112110485703000_78.7.473.29","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020004056"},{"key":"2025112110485703000_78.7.473.30","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018719"},{"key":"2025112110485703000_78.7.473.31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-737361"},{"key":"2025112110485703000_78.7.473.32","doi-asserted-by":"publisher","DOI":"10.1002\/path.5861"},{"key":"2025112110485703000_78.7.473.33","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-03-837039"},{"key":"2025112110485703000_78.7.473.34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-582650"},{"key":"2025112110485703000_78.7.473.35","doi-asserted-by":"publisher","DOI":"10.1038\/ng.518"},{"key":"2025112110485703000_78.7.473.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.04.011"},{"key":"2025112110485703000_78.7.473.37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-496893"},{"key":"2025112110485703000_78.7.473.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.04.004"},{"key":"2025112110485703000_78.7.473.39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801445"},{"key":"2025112110485703000_78.7.473.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.015"},{"key":"2025112110485703000_78.7.473.41","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003535"},{"key":"2025112110485703000_78.7.473.42","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30441-1"},{"key":"2025112110485703000_78.7.473.43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-154013"},{"key":"2025112110485703000_78.7.473.44","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.8762"},{"key":"2025112110485703000_78.7.473.45","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.195818"},{"key":"2025112110485703000_78.7.473.46","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009530"},{"key":"2025112110485703000_78.7.473.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2010.12.016"},{"key":"2025112110485703000_78.7.473.48","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-024-01111-w","article-title":"Identification of genetic subtypes in follicular lymphoma","volume":"14","author":"Shelton","year":"2024","journal-title":"Blood Cancer J"},{"key":"2025112110485703000_78.7.473.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.02.001"},{"key":"2025112110485703000_78.7.473.50","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0134833","article-title":"High Throughput Sequencing Analysis of the Immunoglobulin Heavy Chain Gene from Flow-Sorted B Cell Sub-Populations Define the Dynamics of Follicular Lymphoma Clonal Evolution","volume":"10","author":"Carlotti","year":"2015","journal-title":"PLoS One"},{"key":"2025112110485703000_78.7.473.51","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009855"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp-2024-209880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:49:06Z","timestamp":1763750946000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp-2024-209880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,6,19]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/jcp-2024-209880"],"URL":"https:\/\/doi.org\/10.1136\/jcp-2024-209880","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"type":"print","value":"0021-9746"},{"type":"electronic","value":"1472-4146"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}