Testicular large B‐cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL
Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent <i>in situ</i> hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. <i>BCL6</i> rearrangements were detected in 36% of cases, and no concomitant <i>BCL2</i> and <i>MYC</i> rearrangements were found. TLBCL had fewer copy number alterations (<i>p </i>< 0.04) but more somatic variants (<i>p </i>< 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 (<i>BCL2</i>) gains and 6q and 9p21.3 (<i>CDKN2A/B</i>) deletions. <i>PIM1</i>, <i>MYD88</i> <sup><i>L265P</i></sup> , <i>CD79B</i>, <i>TBL1XR1</i>, <i>MEF2B</i>, <i>CIITA</i>, <i>EP300,</i> and <i>ETV6</i> mutations were more frequent in TLBCL, and <i>BCL10</i> mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.
Authors
- Guillem Clot (ORCID: https://orcid.org/0000-0003-2588-7413)
- Jan Bosch‐Schips (ORCID: https://orcid.org/0009-0009-7888-6810)
- Fina Climent (ORCID: https://orcid.org/0000-0002-4360-8388)
- Stefan Wiemann (ORCID: https://orcid.org/0000-0003-4683-3174)
- Gerard Frigola (ORCID: https://orcid.org/0000-0001-6794-6456)
- Elı́as Campo (ORCID: https://orcid.org/0000-0001-9850-9793)
- Juan M. Sancho‐Cia
- Reiner Siebert (ORCID: https://orcid.org/0000-0001-7433-3703)
- N. Villamor
- Carmen Bárcena (ORCID: https://orcid.org/0000-0002-7470-1446)
- Cristina López (ORCID: https://orcid.org/0000-0001-6644-1659)
- Marta Grau (ORCID: https://orcid.org/0000-0003-3779-0387)
- Alejandro Martı́n (ORCID: https://orcid.org/0000-0001-6330-1028)
- Nicholas Kelleher (ORCID: https://orcid.org/0000-0003-4610-2718)
- Miguel Alcoceba (ORCID: https://orcid.org/0000-0002-3819-4846)
- Eva M. González-Barca (ORCID: https://orcid.org/0000-0002-1323-1508)
- Naveed Ishaque (ORCID: https://orcid.org/0000-0002-8426-901X)
- Eva Giné (ORCID: https://orcid.org/0000-0002-0532-1204)
- Ferran Nadeu (ORCID: https://orcid.org/0000-0003-2910-9440)
- Alfredo Rivas‐Delgado (ORCID: https://orcid.org/0000-0003-0385-3415)
- L. Luizaga (ORCID: https://orcid.org/0000-0001-9314-5783)
- Itziar Salaverría (ORCID: https://orcid.org/0000-0002-2427-9822)
- Josefine Radke (ORCID: https://orcid.org/0000-0001-9860-2007)
- Gustavo Tapia (ORCID: https://orcid.org/0000-0003-1882-0368)
- Sı́lvia Beà (ORCID: https://orcid.org/0000-0001-7192-2385)
- Kennosuke Karube (ORCID: https://orcid.org/0000-0002-1205-858X)
- Frank L. Heppner (ORCID: https://orcid.org/0000-0001-9816-8917)
- Anna Enjuanes (ORCID: https://orcid.org/0000-0002-4679-6687)
- Tycho Baumann (ORCID: https://orcid.org/0000-0003-4421-0088)
- Ana Muntañola
- Jordi A. Brito
- E Matutes
- Armando López‐Guillermo
Institutions
- Universitat Autònoma de Barcelona (ES)
- German Cancer Research Center (DE)
- Universität Ulm (DE)
- Heidelberg University (DE)
- Universitätsmedizin Greifswald (DE)
- Bellvitge University Hospital (ES)
- Humboldt-Universität zu Berlin (DE)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Nagoya University Hospital (JP)
- Hospital Universitario 12 De Octubre (ES)
- German Cancer Society (DE)
- Institut Català d'Oncologia (ES)
- Hospital Clínic de Barcelona (ES)
- Mútua Terrassa (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Centro de Investigación del Cáncer (ES)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Duran i Reynals Hospital (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Hospital Universitari de Girona Doctor Josep Trueta (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Deutsches Konsortium für Translationale Krebsforschung (DE)
- Universitat de Barcelona (ES)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- HemaSphere
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1002/hem3.70024
- Citations
- 8
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.40
Funders
- American Association for Cancer Research
- Eli Lilly and Company
- AstraZeneca
- Gilead Sciences
- Celgene
- European Hematology Association
- Incyte
- Xarxa de Bancs de Tumors de Catalunya
- Kite Pharma
- Instituto de Salud Carlos III
- European Regional Development Fund