Large B-cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma
Mantle cell lymphoma (MCL) is genetically characterized by the IG::CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 rearrangements in these tumors and their genomic profile are not known. We have reconstructed the IG::CCND1 translocations and the genomic profile of 13 SOX11-negative aggressive B-cell lymphomas using whole genome/exome and target sequencing. The mechanism behind the translocation was an aberrant V(D)J rearrangement in three tumors and by an anomalous IGH class-switch recombination (CSR) or somatic hypermutation (SHM) mechanism in ten. The tumors with a V(D)J-mediated translocation were two blastoid MCL and one high-grade B-cell lymphoma. None of them had a mutational profile suggestive of DLBCL. The ten tumors with CSR/SHM-mediated IGH::CCND1 were mainly large B-cell lymphomas, with mutated genes commonly seen in DLBCL and BCL6 rearrangements in 6. Two cases, which transformed from marginal zone lymphomas, carried mutations in KLF2, TNFAIP3 and KMT2D. These findings expand the spectrum of tumors carrying CCND1 rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL.
Authors
- Thorsten Zenz (ORCID: https://orcid.org/0000-0001-7890-9845)
- Jan Bosch‐Schips (ORCID: https://orcid.org/0009-0009-7888-6810)
- Romina Royo (ORCID: https://orcid.org/0000-0003-3493-0874)
- Fina Climent (ORCID: https://orcid.org/0000-0002-4360-8388)
- Olga Balagué (ORCID: https://orcid.org/0000-0002-5099-3675)
- Sílvia Ruiz-Gaspà
- Mark Raffeld (ORCID: https://orcid.org/0000-0002-4039-6957)
- Gerard Frigola (ORCID: https://orcid.org/0000-0001-6794-6456)
- Sylvain Carras
- Elı́as Campo (ORCID: https://orcid.org/0000-0001-9850-9793)
- Pablo Bousquets‐Muñoz (ORCID: https://orcid.org/0000-0002-2969-008X)
- Marco Roncador (ORCID: https://orcid.org/0000-0002-4574-4703)
- Julia Salmerón‐Villalobos (ORCID: https://orcid.org/0000-0002-7092-9160)
- Marco M. Bühler (ORCID: https://orcid.org/0000-0003-0850-3326)
- Cristina López (ORCID: https://orcid.org/0000-0001-6644-1659)
- Charlotte Syrykh (ORCID: https://orcid.org/0000-0002-3201-6109)
- Anna Montaner
- Eva Giné (ORCID: https://orcid.org/0000-0002-0532-1204)
- Séverine Valmary‐Degano (ORCID: https://orcid.org/0000-0001-9836-909X)
- Ferran Nadeu (ORCID: https://orcid.org/0000-0003-2910-9440)
- Ece Özoğul (ORCID: https://orcid.org/0000-0002-8905-0199)
- Dolors Costa (ORCID: https://orcid.org/0000-0002-8276-3292)
- Itziar Salaverría (ORCID: https://orcid.org/0000-0002-2427-9822)
- Laurence de Leval (ORCID: https://orcid.org/0000-0003-3994-516X)
- Sı́lvia Beà (ORCID: https://orcid.org/0000-0001-7192-2385)
- Melina Pol (ORCID: https://orcid.org/0000-0002-4670-4252)
- Elaine S. Jaffe (ORCID: https://orcid.org/0000-0003-4632-0301)
- Xosé S. Puente (ORCID: https://orcid.org/0000-0001-9525-1483)
- Leticia Quintanilla‐Martinez
- Melika Bashiri
- Pierre Brousset
- Alexandra Traverse-Glehen
- Juliette Fontaine
- Luca Giudici
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- National Institutes of Health (US)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Universidad de Oviedo (ES)
- University of Zurich (CH)
- Barcelona Supercomputing Center (ES)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Bellvitge University Hospital (ES)
- Centre Hospitalier Universitaire Vaudois (CH)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Centre Hospitalier Universitaire de Besançon (FR)
- Universitätsklinikum Tübingen (DE)
- Ente Ospedaliero Cantonale (CH)
- Institut universitaire du cancer de Toulouse Oncopole (FR)
- University Hospital of Zurich (CH)
- Hospices Civils de Lyon (FR)
- Laboratoire d'Aérologie (FR)
- Hôpital Lyon Sud (FR)
- Hospital Clínic de Barcelona (ES)
- University Children's Hospital Tübingen (DE)
- National Cancer Institute (US)
- Grenoble Institute of Neurosciences (FR)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Hacettepe University (TR)
- Universitat de Barcelona (ES)
- University of Tübingen (DE)
- Université Grenoble Alpes (FR)
- Universitat Politècnica de Catalunya (ES)
- University of Lausanne (CH)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2024-09-23
- DOI
- https://doi.org/10.1038/s41408-024-01146-z
- Citations
- 8
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.40
Funders
- Generalitat de Catalunya
- Institució Catalana de Recerca i Estudis Avançats
- Ministerio de Ciencia e Innovación
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III