{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:39:08Z","timestamp":1764333548926,"version":"3.44.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7244384"],"award-info":[{"award-number":["7244384"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Peripheral T\u2010cell lymphoma (PTCL) is relatively prevalent in Asian populations. Previous studies suggest that germline mutations in familial haemophagocytic lymphohistiocytosis (FHL)\u2010related genes may predispose individuals to lymphoproliferative disorders. To investigate the underlying molecular mechanisms, we analysed paired tumour and germline deoxyribonucleic acid from 74 patients with T\u2010 and natural killer\u2010cell lymphomas. Germline variants in FHL\u2010related genes (<jats:italic>UNC13D<\/jats:italic>, <jats:italic>PRF1<\/jats:italic>, <jats:italic>STXBP2<\/jats:italic>, <jats:italic>STX11<\/jats:italic>, <jats:italic>SH2D1A<\/jats:italic> and <jats:italic>XIAP<\/jats:italic>) were assessed by whole\u2010exome sequencing, while somatic mutations were analysed by targeted sequencing. A total of 21 germline mutations in FHL\u2010related genes were detected in 14 of 74 patients (18.9%), including mutations in <jats:italic>UNC13D<\/jats:italic> (<jats:italic>N<\/jats:italic>\u2009=\u200911), <jats:italic>STXBP2<\/jats:italic> (<jats:italic>N<\/jats:italic>\u2009=\u20096), <jats:italic>PRF1<\/jats:italic> (<jats:italic>N<\/jats:italic>\u2009=\u20093) and <jats:italic>STX11<\/jats:italic> (<jats:italic>N<\/jats:italic>\u2009=\u20091). The most frequent mutation was <jats:italic>UNC13D<\/jats:italic> c.2588G&gt;A (p.G863D), which was significantly enriched in PTCL patients compared to the general Chinese Han population (allele frequency: 4.7% vs. 0.7%, OR\u2009=\u20096.785, <jats:italic>p<\/jats:italic>\u2009=\u20090.002). In line with established PTCL mutation profiles, somatic mutations were frequently detected in <jats:italic>TET2<\/jats:italic>, <jats:italic>RHOA<\/jats:italic>, <jats:italic>DNMT3A<\/jats:italic> and <jats:italic>IDH2.<\/jats:italic> Patients with FHL\u2010related germline mutations exhibited a trend towards better overall survival. In conclusion, germline mutations in FHL\u2010related genes, particularly <jats:italic>UNC13D<\/jats:italic>, may contribute to PTCL susceptibility in Chinese patients and are associated with clonal somatic mutations.<\/jats:p>","DOI":"10.1111\/bjh.20231","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T02:44:56Z","timestamp":1750733096000},"page":"842-850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Germline defects of familial haemophagocytic lymphohistiocytosis\u2014Related genes may represent a predisposing factor for mature T\u2010 and natural killer\u2010cell lymphoma"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-8555","authenticated-orcid":false,"given":"Chong","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-218X","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-5965","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1592-1932","authenticated-orcid":false,"given":"Daobin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_12_2_1","DOI":"10.1182\/blood\u20102016\u201001\u2010643569"},{"doi-asserted-by":"publisher","key":"e_1_2_12_3_1","DOI":"10.1002\/cam4.3037"},{"doi-asserted-by":"publisher","key":"e_1_2_12_4_1","DOI":"10.1200\/JCO.2008.16.4558"},{"doi-asserted-by":"publisher","key":"e_1_2_12_5_1","DOI":"10.1002\/ajh.24791"},{"doi-asserted-by":"publisher","key":"e_1_2_12_6_1","DOI":"10.1182\/blood-2014-04-573089"},{"doi-asserted-by":"publisher","key":"e_1_2_12_7_1","DOI":"10.1182\/bloodadvances.2021005171"},{"doi-asserted-by":"publisher","key":"e_1_2_12_8_1","DOI":"10.1038\/s41375\u2010019\u20100473\u20101"},{"doi-asserted-by":"publisher","key":"e_1_2_12_9_1","DOI":"10.3324\/haematol.2016.158428"},{"doi-asserted-by":"publisher","key":"e_1_2_12_10_1","DOI":"10.1182\/blood.2019000936"},{"doi-asserted-by":"publisher","key":"e_1_2_12_11_1","DOI":"10.1038\/ni1431"},{"doi-asserted-by":"publisher","key":"e_1_2_12_12_1","DOI":"10.1091\/mbc.e04-10-0923"},{"issue":"5","key":"e_1_2_12_13_1","first-page":"5249","article-title":"Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma","volume":"14","author":"Chen X","year":"2017","journal-title":"Oncol Lett"},{"doi-asserted-by":"publisher","key":"e_1_2_12_14_1","DOI":"10.1007\/s11596-021-2375-5"},{"doi-asserted-by":"publisher","key":"e_1_2_12_15_1","DOI":"10.3389\/fimmu.2024.1365975"},{"doi-asserted-by":"publisher","key":"e_1_2_12_16_1","DOI":"10.1093\/bioinformatics\/btp324"},{"doi-asserted-by":"publisher","key":"e_1_2_12_17_1","DOI":"10.21203\/rs.3.rs\u20102561857\/v1"},{"doi-asserted-by":"publisher","key":"e_1_2_12_18_1","DOI":"10.1371\/journal.pone.0107386"},{"doi-asserted-by":"publisher","key":"e_1_2_12_19_1","DOI":"10.1186\/s13023\u2010020\u201001390\u2010z"},{"doi-asserted-by":"publisher","key":"e_1_2_12_20_1","DOI":"10.1002\/cncr.32011"},{"doi-asserted-by":"publisher","key":"e_1_2_12_21_1","DOI":"10.1080\/10428194.2016.1177724"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.20231","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T02:45:34Z","timestamp":1757990734000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.20231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,23]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/bjh.20231"],"URL":"https:\/\/doi.org\/10.1111\/bjh.20231","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"type":"print","value":"0007-1048"},{"type":"electronic","value":"1365-2141"}],"subject":[],"published":{"date-parts":[[2025,6,23]]},"assertion":[{"value":"2025-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}