PMID- 16705090 OWN - NLM STAT- MEDLINE DCOM- 20061005 LR - 20220331 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 108 IP - 5 DP - 2006 Sep 1 TI - Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma. PG - 1733-43 AB - 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. FAU - Walker, Brian A AU - Walker BA AD - Section of Haemato-Oncology, Institute for Cancer Research, 15 Cotswold Rd, Sutton, Surrey, United Kingdom. FAU - Leone, Paola E AU - Leone PE FAU - Jenner, Matthew W AU - Jenner MW FAU - Li, Cheng AU - Li C FAU - Gonzalez, David AU - Gonzalez D FAU - Johnson, David C AU - Johnson DC FAU - Ross, Fiona M AU - Ross FM FAU - Davies, Faith E AU - Davies FE FAU - Morgan, Gareth J AU - Morgan GJ LA - eng GR - G0100132/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060516 PL - United States TA - Blood JT - Blood JID - 7603509 SB - IM MH - Bone Marrow/pathology MH - *Chromosome Mapping MH - Gene Expression Regulation, Neoplastic MH - Genome, Human MH - Humans MH - Loss of Heterozygosity MH - Multiple Myeloma/*genetics/pathology MH - Oligonucleotide Array Sequence Analysis MH - *Polymorphism, Single Nucleotide MH - Uniparental Disomy/genetics EDAT- 2006/05/18 09:00 MHDA- 2006/10/06 09:00 CRDT- 2006/05/18 09:00 PHST- 2006/05/18 09:00 [pubmed] PHST- 2006/10/06 09:00 [medline] PHST- 2006/05/18 09:00 [entrez] AID - S0006-4971(20)52647-5 [pii] AID - 10.1182/blood-2006-02-005496 [doi] PST - ppublish SO - Blood. 2006 Sep 1;108(5):1733-43. doi: 10.1182/blood-2006-02-005496. Epub 2006 May 16.