IngentaConnect Identification of ID-1 as a potential target gene of MMSET in mul...

Authors: Hudlebusch, Heidi Rye; Theilgaard-Mönch, Kim¹; Lodahl, Marianne²; Johnsen, Hans Erik²; Rasmussen, Thomas²

Source: British Journal of Haematology, Volume 130, Number 5, September 2005 , pp. 700-708(9)

Abstract:

Summary

The frequently detected t(4;14)(p16·3;q32) translocation in multiple myeloma (MM) results in a dysregulation of two potential oncogenes: multiple myeloma SET domain (MMSET) and fibroblast growth factor receptor 3 (FGFR3). As the expression of FGFR3 is undetectable in 30% of the t(4;14)⁺ MM patients, MMSET has been suggested to play an important role in the malignant transformation associated with the t(4;14) translocation. Screening with a real-time polymerase chain reaction (PCR) found complex expression patterns of the MMSET transcripts in fluorescence-activated cell sorted (FACS)-purified plasma cells (PCs) from 15 t(4;14)⁺ MM patients. In addition, potential target genes of MMSET type I and II were identified, using microarray analyses of MMSET transfected cell lines. Subsequently, the expression of potential target genes was verified by real-time PCR in FACS-purified PCs from 15 t(4;14)⁺ and 22 t(4;14)^- MM patients. We suggest that the inhibitor of differentiation 1 (ID-1) is a target gene of MMSET, based on its upregulation in MMSET transfected cell lines and a significant association between the t(4;14) translocation and ID-1 expression in MM patients (P = 0·002). As high levels of ID-1 are associated with cancer, our findings indicate that MMSET promotes oncogenic transformation in t(4;14)⁺ MM patients by transcriptional activation of ID-1 expression.

Keywords: multiple myeloma SET domain (MMSET); fibroblast growth factor receptor 3 (FGFR3); inhibitor of differentiation-1 (ID-1); multiple myeloma; microarray

Document Type: Research article

DOI: 10.1111/j.1365-2141.2005.05664.x

Affiliations: 1: Granulocyte Research Laboratory, Department of Haematology, The Finsen Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2: The Department of Haematology L, Herlev University Hospital, University of Copenhagen, Herlev

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Identification of ID-1 as a potential target gene of MMSET in multiple myeloma