{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:04:53Z","timestamp":1760058293207,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Assignment","award":["124040300006-2"],"award-info":[{"award-number":["124040300006-2"]}]},{"name":"NRC \u201cKurchatov institute\u201d","award":["124040300006-2"],"award-info":[{"award-number":["124040300006-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-grade B-cell lymphoma (HGBL), not otherwise specified (NOS), is a rare entity within the spectrum of B-cell lymphomas. HGBL, NOS remains a diagnosis of exclusion with limited data available on the optimal clinical approach. We report a case of a 67-year-old man with HGBL, NOS with a germinal center B-cell (GCB) immunophenotype. The disease was characterized by an aggressive clinical course, refractory to multiple lines of cytotoxic chemotherapy, immunotargeted treatment, therapy with a PD-1 inhibitor, and haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Ultimately, the disease progression led to the patient\u2019s death nine months post-diagnosis. A FISH assay identified a sole genetic rearrangement: BCL2\/IGH. Whole-exome sequencing revealed a number of significant somatic mutations, such as TP53 p.C238G, B2M p.L12R, STAT6 p.D419G, STAT3 p.S614R, TREX1 p.T49fs, and CREBBP p.C367Ter, as well as a high focal amplification of the MUC3A gene and the deletion of the short arm of chromosome 17 (del(17p)). An inactivating somatic mutation in the TREX1 gene (p.T49fs) has not been previously described in patients with non-Hodgkin lymphomas. Additionally, our analysis uncovered a key cancer hallmark: tumor genomic instability, manifested as a high tumor mutational burden, which likely contributed to the aggressive disease course.<\/jats:p>","DOI":"10.3390\/ijms26072926","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T07:46:50Z","timestamp":1742802410000},"page":"2926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Tumor Mutation Burden (TMB) and a Novel Somatic Mutation in the TREX1 Gene in a Patient with Aggressive and Refractory High-Grade B-Cell Lymphoma: A Case Report"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-9241","authenticated-orcid":false,"given":"Mariia","family":"Gusakova","sequence":"first","affiliation":[{"name":"National Research Center \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-5597","authenticated-orcid":false,"given":"Fedor","family":"Sharko","sequence":"additional","affiliation":[{"name":"National Research Center \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3795-0571","authenticated-orcid":false,"given":"Eugenia","family":"Boulygina","sequence":"additional","affiliation":[{"name":"National Research Center \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"},{"name":"National Medical Research Center for Hematology, 125167 Moscow, Russia"},{"name":"V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Akademika Oparina Street, 4, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Slobodova","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Akademika Oparina Street, 4, 117997 Moscow, Russia"},{"name":"Faculty of Biology and Biotechnology, HSE University, 101000 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5467-2986","authenticated-orcid":false,"given":"Maria","family":"Gladysheva-Azgari","sequence":"additional","affiliation":[{"name":"National Research Center \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"},{"name":"V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Akademika Oparina Street, 4, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darima","family":"Badmazhapova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artem","family":"Bullikh","sequence":"additional","affiliation":[{"name":"Pathology Department, JSC \u201cMedsi\u201d, 143442 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Khestanova","sequence":"additional","affiliation":[{"name":"Pathology Department, JSC \u201cMedsi\u201d, 143442 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelli","family":"Gabeeva","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-652X","authenticated-orcid":false,"given":"Tatiana","family":"Obukhova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Zvonkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, 125167 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Tsygankova","sequence":"additional","affiliation":[{"name":"National Research Center \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"},{"name":"National Medical Research Center for Hematology, 125167 Moscow, Russia"},{"name":"V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Akademika Oparina Street, 4, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1056\/NEJMra2027612","article-title":"Diffuse Large B-Cell Lymphoma","volume":"384","author":"Sehn","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1182\/hematology.2021000247","article-title":"Double-Hit Lymphoma: Optimizing Therapy","volume":"2021","author":"Dunleavy","year":"2021","journal-title":"Hematol. Am. Soc. Hematol. Educ. 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