Cyclin D1-negative mantle cell lymphoma: A clinicopathologic study based on gene expression profiling

Kai Fu, Dennis D. Weisenburger, Timothy C. Greiner, Sandeep Dave, George Wright, Andreas Rosenwald, Michael Chiorazzi, Javeed Iqbal, Stefan Gesk, Reiner Siebert, Daphne De Jong, Elaine S. Jaffe, Wyndham H. Wilson, Jan Delabie, German Ott, Bhavana J. Dave, Warren G. Sanger, Lynette M. Smith, Lisa Rimsza, Rita M. BrazielH. Konrad Müller-Hermelink, Elias Campo, Randy D. Gascoyne, Louis M. Staudt, Wing C. Chan

Research output: Contribution to journalArticle

255 Citations (Scopus)

Abstract

Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases that lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of 6 cases of cyclin D1-negative MCL. All 6 cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL but lacked the t(11;14)(q13; q32) by fluorescence in situ hybridization (FISH) analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (2 cases) or cyclin D3 (4 cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1-negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL.

Original languageEnglish (US)
Pages (from-to)4315-4321
Number of pages7
JournalBlood
Volume106
Issue number13
DOIs
StatePublished - Dec 15 2005
Externally publishedYes

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Mantle-Cell Lymphoma
Cyclin D1
Gene Expression Profiling
Gene expression
Cyclin D3
Cyclin D2
Fluorescence In Situ Hybridization
Transcriptome
Fluorescence
Cyclin D
Genetic Translocation
Interphase
Amplification
Tumors
Proteins
Cells
Up-Regulation
Messenger RNA
Gene Expression

ASJC Scopus subject areas

  • Hematology

Cite this

Fu, K., Weisenburger, D. D., Greiner, T. C., Dave, S., Wright, G., Rosenwald, A., ... Chan, W. C. (2005). Cyclin D1-negative mantle cell lymphoma: A clinicopathologic study based on gene expression profiling. Blood, 106(13), 4315-4321. https://doi.org/10.1182/blood-2005-04-1753

Cyclin D1-negative mantle cell lymphoma : A clinicopathologic study based on gene expression profiling. / Fu, Kai; Weisenburger, Dennis D.; Greiner, Timothy C.; Dave, Sandeep; Wright, George; Rosenwald, Andreas; Chiorazzi, Michael; Iqbal, Javeed; Gesk, Stefan; Siebert, Reiner; De Jong, Daphne; Jaffe, Elaine S.; Wilson, Wyndham H.; Delabie, Jan; Ott, German; Dave, Bhavana J.; Sanger, Warren G.; Smith, Lynette M.; Rimsza, Lisa; Braziel, Rita M.; Müller-Hermelink, H. Konrad; Campo, Elias; Gascoyne, Randy D.; Staudt, Louis M.; Chan, Wing C.

In: Blood, Vol. 106, No. 13, 15.12.2005, p. 4315-4321.

Research output: Contribution to journalArticle

Fu, K, Weisenburger, DD, Greiner, TC, Dave, S, Wright, G, Rosenwald, A, Chiorazzi, M, Iqbal, J, Gesk, S, Siebert, R, De Jong, D, Jaffe, ES, Wilson, WH, Delabie, J, Ott, G, Dave, BJ, Sanger, WG, Smith, LM, Rimsza, L, Braziel, RM, Müller-Hermelink, HK, Campo, E, Gascoyne, RD, Staudt, LM & Chan, WC 2005, 'Cyclin D1-negative mantle cell lymphoma: A clinicopathologic study based on gene expression profiling', Blood, vol. 106, no. 13, pp. 4315-4321. https://doi.org/10.1182/blood-2005-04-1753
Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A et al. Cyclin D1-negative mantle cell lymphoma: A clinicopathologic study based on gene expression profiling. Blood. 2005 Dec 15;106(13):4315-4321. https://doi.org/10.1182/blood-2005-04-1753
Fu, Kai ; Weisenburger, Dennis D. ; Greiner, Timothy C. ; Dave, Sandeep ; Wright, George ; Rosenwald, Andreas ; Chiorazzi, Michael ; Iqbal, Javeed ; Gesk, Stefan ; Siebert, Reiner ; De Jong, Daphne ; Jaffe, Elaine S. ; Wilson, Wyndham H. ; Delabie, Jan ; Ott, German ; Dave, Bhavana J. ; Sanger, Warren G. ; Smith, Lynette M. ; Rimsza, Lisa ; Braziel, Rita M. ; Müller-Hermelink, H. Konrad ; Campo, Elias ; Gascoyne, Randy D. ; Staudt, Louis M. ; Chan, Wing C. / Cyclin D1-negative mantle cell lymphoma : A clinicopathologic study based on gene expression profiling. In: Blood. 2005 ; Vol. 106, No. 13. pp. 4315-4321.
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abstract = "Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases that lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of 6 cases of cyclin D1-negative MCL. All 6 cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL but lacked the t(11;14)(q13; q32) by fluorescence in situ hybridization (FISH) analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (2 cases) or cyclin D3 (4 cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1-negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL.",
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AU - Fu, Kai

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy C.

AU - Dave, Sandeep

AU - Wright, George

AU - Rosenwald, Andreas

AU - Chiorazzi, Michael

AU - Iqbal, Javeed

AU - Gesk, Stefan

AU - Siebert, Reiner

AU - De Jong, Daphne

AU - Jaffe, Elaine S.

AU - Wilson, Wyndham H.

AU - Delabie, Jan

AU - Ott, German

AU - Dave, Bhavana J.

AU - Sanger, Warren G.

AU - Smith, Lynette M.

AU - Rimsza, Lisa

AU - Braziel, Rita M.

AU - Müller-Hermelink, H. Konrad

AU - Campo, Elias

AU - Gascoyne, Randy D.

AU - Staudt, Louis M.

AU - Chan, Wing C.

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N2 - Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases that lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of 6 cases of cyclin D1-negative MCL. All 6 cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL but lacked the t(11;14)(q13; q32) by fluorescence in situ hybridization (FISH) analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (2 cases) or cyclin D3 (4 cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1-negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL.

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