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