title: A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value.
abstract: To obtain a comprehensive genomic profile of presenting multiple myeloma cases we performed high-resolution single nucleotide polymorphism mapping array analysis in 114 samples alongside 258 samples analyzed by U133 Plus 2.0 expression array (Affymetrix). We examined DNA copy number alterations and loss of heterozygosity (LOH) to define the spectrum of minimally deleted regions in which relevant genes of interest can be found. The most frequent deletions are located at 1p (30%), 6q (33%), 8p (25%), 12p (15%), 13q (59%), 14q (39%), 16q (35%), 17p (7%), 20 (12%), and 22 (18%). In addition, copy number-neutral LOH, or uniparental disomy, was also prevalent on 1q (8%), 16q (9%), and X (20%), and was associated with regions of gain and loss. Based on fluorescence in situ hybridization and expression quartile analysis, genes of prognostic importance were found to be located at 1p (FAF1, CDKN2C), 1q (ANP32E), and 17p (TP53). In addition, we identified common homozygously deleted genes that have functions relevant to myeloma biology. Taken together, these analyses indicate that the crucial pathways in myeloma pathogenesis include the nuclear factor-κB pathway, apoptosis, cell-cycle regulation, Wnt signaling, and histone modifications. This study was registered at http://isrctn.org as ISRCTN68454111.
authors.affiliation: Section of Haemato-Oncology, The Institute of Cancer Research, London, UK. brian.walker@icr.ac.uk
authors.forename: Brian A
authors.initials: BA
authors.lastname: Walker
authors.forename: Paola E
authors.initials: PE
authors.lastname: Leone
authors.forename: Laura
authors.initials: L
authors.lastname: Chiecchio
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Dickens
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Jenner
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Boyd
authors.forename: David C
authors.initials: DC
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Dagrada
authors.forename: Rebecca K M
authors.initials: RK
authors.lastname: Protheroe
authors.forename: Zoe J
authors.initials: ZJ
authors.lastname: Konn
authors.forename: David M
authors.initials: DM
authors.lastname: Stockley
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000368:Aged; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D014178:Translocation, Genetic; D024182:Uniparental Disomy