{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:51:46Z","timestamp":1793681506005,"version":"4.5.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"Abstract<\/jats:title>\n \n Recent studies highlighted genetic aberrations associated with prognosis in Mantle Cell lymphoma (MCL), yet comprehensive testing is not implemented in clinical routine. We conducted a comprehensive genomic characterization of 180 patients from the\u00a0European MCL network trials by targeted sequencing of peripheral blood DNA using the EuroClonality(EC)-NDC assay. The\n IGH::CCND1<\/jats:italic>\n fusion was identified in 94% of patients, clonal IGH-V-(D)-J rearrangements in all, and 79% had \u22651 somatic gene mutation. The top mutated genes were\n ATM<\/jats:italic>\n ,\n TP53<\/jats:italic>\n ,\n KMT2D<\/jats:italic>\n ,\n SAMHD1<\/jats:italic>\n ,\n BIRC3<\/jats:italic>\n and\n NFKBIE<\/jats:italic>\n . Copy number variations (CNVs) were detected in 83% of patients with\n RB1<\/jats:italic>\n ,\n ATM<\/jats:italic>\n ,\n CDKN2A\/B<\/jats:italic>\n and\n TP53<\/jats:italic>\n being the most frequently\u00a0deleted and\n KLF2<\/jats:italic>\n ,\n CXCR4<\/jats:italic>\n ,\n CCND1<\/jats:italic>\n ,\n MAP2K1<\/jats:italic>\n and\n MYC<\/jats:italic>\n the top amplified genes. CNVs and mutations were more frequently observed in older patients with adverse impact on prognosis.\n TP53<\/jats:italic>\n \n mut<\/jats:italic>\n <\/jats:sup>\n ,\n NOTCH1<\/jats:italic>\n \n mut<\/jats:italic>\n <\/jats:sup>\n , FAT1<\/jats:italic>\n \n mut<\/jats:italic>\n <\/jats:sup>\n TRAF2<\/jats:italic>\n del<\/jats:sup>\n ,\n CDKN2A\/B<\/jats:italic>\n \n del<\/jats:italic>\n <\/jats:sup>\n and\n MAP2K1<\/jats:italic>\n \n amp<\/jats:italic>\n <\/jats:sup>\n were linked to\u00a0inferior failure-free (FFS)\u00a0and overall survival (OS), while\n TRAF2<\/jats:italic>\n mut<\/jats:sup>\n ,\n EGR2<\/jats:italic>\n \n del<\/jats:italic>\n <\/jats:sup>\n and\n BCL2<\/jats:italic>\n \n amp<\/jats:italic>\n <\/jats:sup>\n related\u00a0to inferior OS only. Genetic complexity (\u22653 CNVs) observed in 51% of analysed patients was significantly\u00a0associated with impaired FFS and OS. We demonstrate that targeted sequencing from peripheral blood and bone marrow reliably\u00a0detects diagnostically and prognostically important genetic factors in MCL patients, facilitating genetic characterization in clinical routine.\n <\/jats:p>","DOI":"10.1038\/s41375-024-02375-8","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T03:02:33Z","timestamp":1726455753000},"page":"2675-2684","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials"],"prefix":"10.1038","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9892-9461","authenticated-orcid":false,"given":"Mouhamad","family":"Khouja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-4236","authenticated-orcid":false,"given":"Linmiao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-4691","authenticated-orcid":false,"given":"Karol","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter James","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2663-0983","authenticated-orcid":false,"given":"Binaya","family":"Regmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-4117","authenticated-orcid":false,"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6825-702X","authenticated-orcid":false,"given":"Stefan K.","family":"Alig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Darzentas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke C.","family":"Kluin-Nelemans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Hermine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dreyling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0580-5636","authenticated-orcid":false,"given":"David","family":"Gonzalez de Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-1389","authenticated-orcid":false,"given":"Eva","family":"Hoster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9260-8340","authenticated-orcid":false,"given":"Christiane","family":"Pott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the European Mantle Cell Lymphoma Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"2375_CR1","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1038\/sj.leu.2402272","volume":"15","author":"M Bernard","year":"2001","unstructured":"Bernard M, Gressin R, Lefr\u00e8re F, Dr\u00e9nou B, Branger B, Caulet-Maugendre S, et al. 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Genomics Ltd.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Both clinical trials were led according to the Declaration of Helsinki. All patients gave their written informed consent after have been informed about the purpose and investigational nature of the trial. Prior to initiation, the clinical trial including molecular analysis received approval by the ethics committee of the medical faculty of the Christian-Albrechts-University of Kiel, Germany with the reference number B226\/04.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}