Large B-cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma

• Published in: Blood cancer journal (New York) Vol. 14; no. 1; pp. 166 - 10
• Main Authors: Özoğul, Ece, Montaner, Anna, Pol, Melina, Frigola, Gerard, Balagué, Olga, Syrykh, Charlotte, Bousquets-Muñoz, Pablo, Royo, Romina, Fontaine, Juliette, Traverse-Glehen, Alexandra, Bühler, Marco M., Giudici, Luca, Roncador, Marco, Zenz, Thorsten, Carras, Sylvain, Valmary-Degano, Severine, de Leval, Laurence, Bosch-Schips, Jan, Climent, Fina, Salmeron-Villalobos, Julia, Bashiri, Melika, Ruiz-Gaspà, Silvia, Costa, Dolors, Beà, Sílvia, Salaverria, Itziar, Giné, Eva, Quintanilla-Martinez, Leticia, Brousset, Pierre, Raffeld, Mark, Jaffe, Elaine S., Puente, Xose S., López, Cristina, Nadeu, Ferran, Campo, Elias
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.09.2024; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/51; 45/23; 692/420/755; 692/699/1541/1990/291/1621/1915; Aged; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromosome Breakpoints; Cyclin D1 - genetics; Female; Gene Rearrangement; Genes, Immunoglobulin; Hematology; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - pathology; Male; Middle Aged; Oncology; Translocation, Genetic; V(D)J Recombination - genetics
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-024-01146-z

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.