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Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma.

Authors: Bergsagel, PL  Kuehl, WM  Zhan, F  Sawyer, J  Barlogie, B  Shaughnessy J, JR 
Citation: Bergsagel PL, etal., Blood. 2005 Jul 1;106(1):296-303. Epub 2005 Mar 8.
Pubmed: (View Article at PubMed) PMID:15755896
DOI: Full-text: DOI:10.1182/blood-2005-01-0034

Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and premalignant monoclonal gammopathy of undetermined significance (MGUS) tumors: a nonhyperdiploid pathway associated with a high prevalence of IgH translocations and a hyperdiploid pathway associated with multiple trisomies of 8 chromosomes. Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity. Translocations can directly dysregulate CCND1 (11q13) or CCND3 (6p21), or MAF (16q23) or MAFB (20q11) transcription factors that target CCND2. Biallelic dysregulation of CCND1 occurs in nearly 40% of tumors, most of which are hyperdiploid. Other tumors express increased CCND2, either with or without a t(4;14) translocation. Using gene expression profiling to identify 5 recurrent translocations, specific trisomies, and expression of cyclin D genes, MM tumors can be divided into 8 TC (translocation/cyclin D) groups (11q13, 6p21, 4p16, maf, D1, D1+D2, D2, and none) that appear to be defined by early, and perhaps initiating, oncogenic events. However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor.

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CRRD Object Information
CRRD ID: 1581171
Created: 2006-09-19
Species: All species
Last Modified: 2006-09-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.