title: In multiple myeloma, 14q32 translocations are nonrandom chromosomal fusions driving high expression levels of the respective partner genes.
abstract: In studies of patients with multiple myeloma (MM), gene expression profiling (GEP) of myeloma cells demonstrates substantially higher expression of MMSET, FGFR3, CCND3, CCND1, MAF, and MAFB--the partner genes of 14q32 translocations--than GEP of plasma cells from healthy individuals. Interphase fluorescent in situ hybridization (FISH) was used to discriminate between chromosomal translocations involving different regions of the immunoglobulin heavy chain (IGH) genes at 14q32. With special probes designed for the constant region (IGHC) and the variable region (IGHV), IGH translocations were shown to be definite, nonrandom chromosomal fusions of IGHC with the loci of FGFR3, CCND1, CCND3, MAF, and MAFB genes; and IGHV with the locus of MMSET gene. When correlated with GEP results, the IGH translocations were found to drive expression levels of the partner genes to significantly higher levels (spikes) than copy-number variations. Hence, 42% of IGH translocations were identified among newly diagnosed MM patients (448/1,060). As GEP has become essential for assessing cancer risk, this novel approach is highly consistent with the cytogenetic features of the chromosomal translocations to effectively stratify molecular subgroups of MM on the basis of gene expression profiles of the IGH translocation partner genes in myeloma cells. © 2014 Wiley Periodicals, Inc.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W. Markham St, Little Rock, AR, 72205.
authors.forename: Erming
authors.initials: E
authors.lastname: Tian
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Sawyer
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Heuck
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Joshua
authors.initials: J
authors.lastname: Epstein
mesh_terms: D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D020869:Gene Expression Profiling; D050939:Gene Fusion; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic