TY - JOUR
T1 - Cyclin D1-negative mantle cell lymphoma
T2 - A clinicopathologic study based on gene expression profiling
AU - Fu, Kai
AU - Weisenburger, Dennis D.
AU - Greiner, Timothy Charles
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.
PY - 2005/12/15
Y1 - 2005/12/15
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.
AB - 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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U2 - 10.1182/blood-2005-04-1753
DO - 10.1182/blood-2005-04-1753
M3 - Article
C2 - 16123218
AN - SCOPUS:28844449677
SN - 0006-4971
VL - 106
SP - 4315
EP - 4321
JO - Blood
JF - Blood
IS - 13
ER -