Walker, B. A., Leone, P. E., Jenner, M. W., Li, C., Gonzalez, D., Johnson, D. C., Ross, F. M., Davies, F. E., Morgan, G. 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). pp. 1733-1743. ISSN 0006-4971

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Abstract

Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (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 fluorescence in situ hybridization (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 monoclonal gammopathy of unknown significance (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.

Item Type:	Article
Authors (ICR Faculty only):	Davies, Faith and Morgan, Gareth
All Authors:	Walker, B. A., Leone, P. E., Jenner, M. W., Li, C., Gonzalez, D., Johnson, D. C., Ross, F. M., Davies, F. E., Morgan, G. J.
Uncontrolled Keywords:	In-situ hybridization; comparative genomic hybridization; tumor-suppressor genes; urinary-bladder cancer; uniparental disomy; undetermined significance; hepatocellular-carcinoma; monoclonal gammopathy; interphase fish; breast-cancer
Research teams:	ICR divisions > Clinical Studies > Molecular Haematology (including Cytogenetics Group and Cell Markers) ICR divisions > Molecular Pathology > Molecular Haematology (including Cytogenetics Group and Cell Markers) Clinical Units > Haemato-Oncology Unit Closed research groups > Myeloma Targeted Treatment
Date Deposited:	10 Aug 2007 20:57
Last Modified:	16 Nov 2015 11:37
URI:	http://publications.icr.ac.uk/id/eprint/2971

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