CCND2 rearrangements are the most frequent genetic events in cyclin D1− mantle cell lymphoma

• Published in: Blood Vol. 121; no. 8; pp. 1394 - 1402
• Main Authors: Salaverria, Itziar, Royo, Cristina, Carvajal-Cuenca, Alejandra, Clot, Guillem, Navarro, Alba, Valera, Alejandra, Song, Joo Y., Woroniecka, Renata, Rymkiewicz, Grzegorz, Klapper, Wolfram, Hartmann, Elena M., Sujobert, Pierre, Wlodarska, Iwona, Ferry, Judith A., Gaulard, Philippe, Ott, German, Rosenwald, Andreas, Lopez-Guillermo, Armando, Quintanilla-Martinez, Leticia, Harris, Nancy L., Jaffe, Elaine S., Siebert, Reiner, Campo, Elias, Beà, Sílvia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2013; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin D2 - genetics; Cyclin D2 - metabolism; Cyclin D3 - genetics; Cyclin D3 - metabolism; DNA Copy Number Variations - genetics; DNA Mutational Analysis; Female; Gene Rearrangement - genetics; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoid Neoplasia; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - metabolism; Lymphoma, Mantle-Cell - pathology; Male; Middle Aged; RNA, Messenger - genetics; SOXC Transcription Factors - genetics; SOXC Transcription Factors - metabolism; Translocation, Genetic - genetics
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-08-452284

Cyclin D1− mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1− variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1− SOX11+ MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1+/SOX11+ MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1− MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1+ MCL and provides a basis for the proper identification and clinical management of these patients. •This report describes a multidisciplinary study characterizing the largest series of cyclin D1− MCL patients.•CCND2 translocations are the most frequent genetic event (55%) in cyclin D1− MCL.