title: The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma.
abstract: Aneuploid is ubiquitous in multiple myeloma (MM), and 4 cytogenetic subcategories are recognized: hypodiploid (associated with a shorter survival), pseudodiploid, hyperdiploid, and near-tetraploid MM. The hypodiploid, pseudodiploid, and near-tetraploid karyotypes can be referred to as the nonhyperdiploid MM. Immunoglobulin heavy-chain (IgH) translocations are seen in 60% of patients. We studied the relation between aneuploidy and IgH translocations in MM. Eighty patients with MM and abnormal metaphases were studied by means of interphase fluorescent in situ hybridization (FISH) to detect IgH translocations. We also studied a second cohort of 199 patients (Eastern Cooperative Oncology Group [ECOG]) for IgH translocations, chromosome 13 monosomy/deletions (Delta13), and ploidy by DNA content. Mayo Clinic patients with abnormal karyotypes and FISH-detected IgH translocation were more likely to be nonhyperdiploid (89% versus 39%, P <.0001). Remarkably, 88% of tested patients with hypodiploidy (16 of 18) and 90% of tested patients with tetraploidy (9 of 10) had an IgH translocation. ECOG patients with IgH translocations were more likely to have nonhyperdiploid MM by DNA content (68% versus 21%, P <.001). This association was seen predominantly in patients with recurrent chromosome partners to the IgH translocation (11q13, 4p16, and 16q23). The classification of MM into hyperdiploidy and nonhyperdiploidy is dictated largely by the recurrent (primary) IgH translocations in the latter.
authors.affiliation: Mayo Clinic Division of Hematology, The Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. fonseca.rafael@mayo.edu
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Carina S
authors.initials: CS
authors.lastname: Debes-Marun
authors.forename: Elisa B
authors.initials: EB
authors.lastname: Picken
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Bryant
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Winkler
authors.forename: Emily
authors.initials: E
authors.lastname: Blood
authors.forename: Martin M
authors.initials: MM
authors.lastname: Oken
authors.forename: Rafael
authors.initials: R
authors.lastname: Santana-Dávila
authors.forename: Natalia
authors.initials: N
authors.lastname: González-Paz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
mesh_terms: D000782:Aneuploidy; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009006:Monosomy; D009101:Multiple Myeloma / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D014178:Translocation, Genetic / Q000235:genetics*; D014314:Trisomy
chemical_list: D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains