{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:07:34Z","timestamp":1790665654489,"version":"4.1.0"},"reference-count":62,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typically affects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas with gene expression features of PMBL have been described in nonmediastinal sites, raising questions about how these tumors should be classified. Here, we investigated whether these nonmediastinal lymphomas are indeed PMBLs or instead represent a distinct group within diffuse large B-cell lymphoma (DLBCL). From a cohort of 325 de novo DLBCL cases, we identified tumors from patients without evidence of anterior mediastinal involvement that expressed a PMBL expression signature (nm-PMBLsig+; n = 16; 5%). A majority of these tumors expressed MAL and CD23, proteins typically observed in bona fide PMBL (bf-PMBL). Evaluation of clinical features of nm-PMBLsig+ cases revealed close associations with DLBCL, and a majority displayed a germinal center B cell\u2013like cell of origin (GCB). In contrast to patients with bf-PMBL, patients with nm-PMBLsig+ presented at an older age and did not show pleural disease, and bone\/bone marrow involvement was observed in 3 cases. However, although clinically distinct from bf-PMBL, nm-PMBLsig+ tumors resembled bf-PMBL at the molecular level, with upregulation of immune response, JAK-STAT, and NF-\u03baB signatures. Mutational analysis revealed frequent somatic gene mutations in SOCS1, IL4R, ITPKB, and STAT6, as well as CD83 and BIRC3, with the latter genes significantly more frequently affected than in GCB DLBCL or bf-PMBL. Our data establish nm-PMBLsig+ lymphomas as a group within DLBCL with distinct phenotypic and genetic features. These findings may have implications for gene expression\u2013 and mutation-based subtyping of aggressive B-cell lymphomas and related targeted therapies.<\/jats:p>","DOI":"10.1182\/blood.2020007683","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T22:05:42Z","timestamp":1615241142000},"page":"136-148","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":34,"title":["Characterization of DLBCL with a PMBL gene expression signature"],"prefix":"10.1182","volume":"138","author":[{"given":"Gerben","family":"Duns","sequence":"first","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ennishi","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementine","family":"Sarkozy","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"},{"name":"Early Phase Clinical Trial Department, Institut Gustave Roussy, Villejuif, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy S.","family":"Hung","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Chavez","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Takata","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6306-9361","authenticated-orcid":false,"given":"Christopher","family":"Rushton","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aixiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-4037","authenticated-orcid":false,"given":"Susana","family":"Ben-Neriah","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce W.","family":"Woolcock","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham W.","family":"Slack","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Hsi","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1295-3258","authenticated-orcid":false,"given":"Jeffrey W.","family":"Craig","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-6586","authenticated-orcid":false,"given":"Laura K.","family":"Hilton","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"},{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-523X","authenticated-orcid":false,"given":"Sohrab P.","family":"Shah","sequence":"additional","affiliation":[{"name":"Molecular Oncology and"},{"name":"Canada\u2019s Michael Smith Genome Sciences Centre, British Columbia Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-9391","authenticated-orcid":false,"given":"Pedro","family":"Farinha","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Mottok","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"},{"name":"Institute of Human Genetics, Ulm University Medical Center, Ulm University, Ulm, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy D.","family":"Gascoyne","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-7800","authenticated-orcid":false,"given":"Ryan D.","family":"Morin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;"},{"name":"Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-9863","authenticated-orcid":false,"given":"Kerry J.","family":"Savage","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0435-5947","authenticated-orcid":false,"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"Centre for Lymphoid Cancer, BC Cancer, Vancouver, BC, 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