Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling.
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.
Fu
Kai
K
Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA. kfu@unmc.edu
Weisenburger
Dennis D
DD
Greiner
Timothy C
TC
Dave
Sandeep
S
Wright
George
G
Rosenwald
Andreas
A
Chiorazzi
Michael
M
Iqbal
Javeed
J
Gesk
Stefan
S
Siebert
Reiner
R
De Jong
Daphne
D
Jaffe
Elaine S
ES
Wilson
Wyndham H
WH
Delabie
Jan
J
Ott
German
G
Dave
Bhavana J
BJ
Sanger
Warren G
WG
Smith
Lynette M
LM
Rimsza
Lisa
L
Braziel
Rita M
RM
Müller-Hermelink
H Konrad
HK
Campo
Elias
E
Gascoyne
Randy D
RD
Staudt
Louis M
LM
Chan
Wing C
WC
D019938:Cyclin D1 / Q000172:deficiency* / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology*
D019938:Cyclin D1