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Comprehensive Genome-Wide Profile of Regional Gains and Losses in Multiple Myeloma Using Array-CGH: The 1q21 Amplification and Potential Role of the BCL-9 Gene in Multiple Myeloma Pathogenesis

Authors :
John D. Shaughnessy
Peter Leif Bergsagel
Giovanni Tonon
Ronald A. DePinho
Raktim Sinha
Ruben D. Carrasco
Marina Protopopova
Christopher Leo
Alexei Protopopov
Jean Zhang
Lynda Chin
Kenneth C. Anderson
Nikhil C. Munshi
Yunyu Zhang
Fenghuang Zhan
Bin Feng
Cameron Brennan
Michael Kuehl
Constantine S. Mitsiades
Source :
Blood. 104:785-785
Publication Year :
2004
Publisher :
American Society of Hematology, 2004.

Abstract

Multiple Myeloma (MM) is characterized by a clonal proliferation of abnormal plasma cells in the bone marrow and is among the most frequent and lethal hematological diseases. In spite of significant effort towards the identification of the molecular events leading to this malignancy, the genetic alterations responsible for the pathogenesis of this disease remain poorly understood. Regional copy number alterations (CNAs) in cancer genomes have been among the most informative structural changes in cancer and have led to the discovery of many oncogenes and tumor supressor genes. Using array comparative genomic hybridization (array-CGH) and expression microarray technologies we have analyzed a large collection of cell lines and clinically annotated primary tumors. This high-resolution genomic analysis has identified all previously reported regional gains and losses as well as many novel highly recurrent genetic loci with potential biological and clinical relevance. In particular, we have identified an amplification at chromosome 1q21 as one of the most recurrent genetic changes in cell lines and in a subgroup of primary tumors. This chromosomal change has been previously implicated with disease progression. Analysis across several cell lines has allowed the identification of a Minimal Common Region (MCRs) of amplification at 1q21. Correlation between DNA copy number changes and expression profiling data has identified a limited set of candidate genes within this MCR that are amplified and overexpressed. Using shRNAi technology we have identified BCL-9 as a candidate gene residing at the 1q21 MCR. In vitro and in vivo functional data about the role of BL-9 will be presented. These data will provide critical understanding on the diverse pathways leading to Multiple Myeloma progression.

Details

ISSN :
15280020 and 00064971
Volume :
104
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi...........83e491c764e7aab61bfb5547d3778571
Full Text :
https://doi.org/10.1182/blood.v104.11.785.785