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

Itziar Salaverria, Cristina Royo, Alejandra Carvajal-Cuenca, Guillem Clot, Alba Navarro, Alejandra Valera, Joo Y. Song, Renata Woroniecka, Grzegorz Rymkiewicz, Wolfram Klapper, Elena M. Hartmann, Pierre Sujobert, Iwona Wlodarska, Judith A. Ferry, Philippe Gaulard, German Ott, Andreas Rosenwald, Armando Lopez-Guillermo, Leticia Quintanilla-Martinez, Nancy L. HarrisElaine S. Jaffe, Reiner Siebert, Elias Campo, Sílvia Bea

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1394-1402
Number of pages9
JournalBlood
Volume121
Issue number8
DOIs
StatePublished - Feb 21 2013
Externally publishedYes

Fingerprint

Mantle-Cell Lymphoma
Cyclin D1
Tumors
Phosphorylation
Biomarkers
Lymphoma
Neoplasms
Genes
Light
Mutation
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Salaverria, I., Royo, C., Carvajal-Cuenca, A., Clot, G., Navarro, A., Valera, A., ... Bea, S. (2013). CCND2 rearrangements are the most frequent genetic events in cyclin D1 - mantle cell lymphoma. Blood, 121(8), 1394-1402. https://doi.org/10.1182/blood-2012-08-452284

CCND2 rearrangements are the most frequent genetic events in cyclin D1 - mantle cell lymphoma. / 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; Bea, Sílvia.

In: Blood, Vol. 121, No. 8, 21.02.2013, p. 1394-1402.

Research output: Contribution to journalArticle

Salaverria, I, Royo, C, Carvajal-Cuenca, A, Clot, G, Navarro, A, Valera, A, Song, JY, Woroniecka, R, Rymkiewicz, G, Klapper, W, Hartmann, EM, Sujobert, P, Wlodarska, I, Ferry, JA, Gaulard, P, Ott, G, Rosenwald, A, Lopez-Guillermo, A, Quintanilla-Martinez, L, Harris, NL, Jaffe, ES, Siebert, R, Campo, E & Bea, S 2013, 'CCND2 rearrangements are the most frequent genetic events in cyclin D1 - mantle cell lymphoma', Blood, vol. 121, no. 8, pp. 1394-1402. https://doi.org/10.1182/blood-2012-08-452284
Salaverria I, Royo C, Carvajal-Cuenca A, Clot G, Navarro A, Valera A et al. CCND2 rearrangements are the most frequent genetic events in cyclin D1 - mantle cell lymphoma. Blood. 2013 Feb 21;121(8):1394-1402. https://doi.org/10.1182/blood-2012-08-452284
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 ; Bea, Sílvia. / CCND2 rearrangements are the most frequent genetic events in cyclin D1 - mantle cell lymphoma. In: Blood. 2013 ; Vol. 121, No. 8. pp. 1394-1402.
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T1 - CCND2 rearrangements are the most frequent genetic events in cyclin D1 - mantle cell lymphoma

AU - Salaverria, Itziar

AU - Royo, Cristina

AU - Carvajal-Cuenca, Alejandra

AU - Clot, Guillem

AU - Navarro, Alba

AU - Valera, Alejandra

AU - Song, Joo Y.

AU - Woroniecka, Renata

AU - Rymkiewicz, Grzegorz

AU - Klapper, Wolfram

AU - Hartmann, Elena M.

AU - Sujobert, Pierre

AU - Wlodarska, Iwona

AU - Ferry, Judith A.

AU - Gaulard, Philippe

AU - Ott, German

AU - Rosenwald, Andreas

AU - Lopez-Guillermo, Armando

AU - Quintanilla-Martinez, Leticia

AU - Harris, Nancy L.

AU - Jaffe, Elaine S.

AU - Siebert, Reiner

AU - Campo, Elias

AU - Bea, Sílvia

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N2 - 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.

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