Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms and genes important in the pathogenesis of multiple myeloma

Walker, Brian A., Leone, Paola E., Jenner, Matthew W., Li, Cheng, Gonzalez, David, Johnson, David C., Ross, Fiona M., Davies, Faith E. and Morgan, Gareth J. (2006) Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms and genes important in the pathogenesis of multiple myeloma. Blood, 108 (5), 1733-1743. (doi:10.1182/blood-2006-02-005496).

Abstract

Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. SNP-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and uniparental disomy (UPD). We have found that SNP-based mapping array data and FISH copy number data correlated well, making the technique robust as a tool to investigate myeloma genomics.
The most frequently identified alterations are located at 1p, 1q, 6q, 8p, 13, and 16q. LOH is found in these large regions and also in smaller regions throughout the genome with a median size of 1 Mb. We have identified that UPD is prevalent in myeloma and occurs through a number of mechanisms including mitotic nondisjunction and mitotic recombination. For the first time in myeloma, integration of mapping and expression data has allowed us to reduce the complexity of standard gene expression data and identify candidate genes important in both the transition from normal to MGUS to myeloma and in different subgroups within myeloma. We have documented these genes providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma.

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