PMID- 16123218 OWN - NLM STAT- MEDLINE DCOM- 20060106 LR - 20220316 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 106 IP - 13 DP - 2005 Dec 15 TI - Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. PG - 4315-21 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. FAU - Fu, Kai AU - Fu K AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA. kfu@unmc.edu FAU - Weisenburger, Dennis D AU - Weisenburger DD FAU - Greiner, Timothy C AU - Greiner TC FAU - Dave, Sandeep AU - Dave S FAU - Wright, George AU - Wright G FAU - Rosenwald, Andreas AU - Rosenwald A FAU - Chiorazzi, Michael AU - Chiorazzi M FAU - Iqbal, Javeed AU - Iqbal J FAU - Gesk, Stefan AU - Gesk S FAU - Siebert, Reiner AU - Siebert R FAU - De Jong, Daphne AU - De Jong D FAU - Jaffe, Elaine S AU - Jaffe ES FAU - Wilson, Wyndham H AU - Wilson WH FAU - Delabie, Jan AU - Delabie J FAU - Ott, German AU - Ott G FAU - Dave, Bhavana J AU - Dave BJ FAU - Sanger, Warren G AU - Sanger WG FAU - Smith, Lynette M AU - Smith LM FAU - Rimsza, Lisa AU - Rimsza L FAU - Braziel, Rita M AU - Braziel RM FAU - Muller-Hermelink, H Konrad AU - Muller-Hermelink HK FAU - Campo, Elias AU - Campo E FAU - Gascoyne, Randy D AU - Gascoyne RD FAU - Staudt, Louis M AU - Staudt LM FAU - Chan, Wing C AU - Chan WC CN - Lymphoma/Leukemia Molecular Profiling Project LA - eng GR - CA36727/CA/NCI NIH HHS/United States GR - CA84967/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20050825 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 136601-57-5 (Cyclin D1) SB - IM MH - Cyclin D1/*deficiency/genetics MH - *Gene Expression Profiling MH - Humans MH - Lymphoma, Mantle-Cell/*genetics/immunology/*pathology PMC - PMC1895253 EDAT- 2005/08/27 09:00 MHDA- 2006/01/07 09:00 PMCR- 2006/12/15 CRDT- 2005/08/27 09:00 PHST- 2005/08/27 09:00 [pubmed] PHST- 2006/01/07 09:00 [medline] PHST- 2005/08/27 09:00 [entrez] PHST- 2006/12/15 00:00 [pmc-release] AID - S0006-4971(20)67749-7 [pii] AID - 4315 [pii] AID - 10.1182/blood-2005-04-1753 [doi] PST - ppublish SO - Blood. 2005 Dec 15;106(13):4315-21. doi: 10.1182/blood-2005-04-1753. Epub 2005 Aug 25.