title: Both IGH translocations and chromosome 13q deletions are early events in monoclonal gammopathy of undetermined significance and do not evolve during transition to multiple myeloma.
abstract: Molecular and genetic events associated with the transition from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are still poorly characterized. We investigated serial bone marrow specimens from 11 patients with MGUS who eventually progressed to MM (MM post-MGUS) by interphase fluorescence in situ hybridization for immunoglobulin heavy-chain gene (IgH) translocations and chromosome 13q deletions (del(13q)). In nine patients, IgH translocations were present both in MGUS and MM post-MGUS plasma cells, including three t(11;14)(q13;q32) and one t(4;14)(p16;q32), which was observed already 92 months prior to MM. Similarly, all five MM patients with del(13q) had this aberration already at the MGUS stage. Two patients without IgH translocation and del(13q) had chromosomal gains suggesting hyperdiploidy, but IgH translocations and/or del(13q) did not emerge at MM post-MGUS. IgH translocations and del(13q) are early genetic events in monoclonal gammopathies, suggesting that additional events are required for the transition from stable MGUS to progressive MM.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Kaufmann
authors.forename: J
authors.initials: J
authors.lastname: Ackermann
authors.forename: C
authors.initials: C
authors.lastname: Baldia
authors.forename: T
authors.initials: T
authors.lastname: Nösslinger
authors.forename: R
authors.initials: R
authors.lastname: Wieser
authors.forename: S
authors.initials: S
authors.lastname: Seidl
authors.forename: V
authors.initials: V
authors.lastname: Sagaster
authors.forename: H
authors.initials: H
authors.lastname: Gisslinger
authors.forename: U
authors.initials: U
authors.lastname: Jäger
authors.forename: M
authors.initials: M
authors.lastname: Pfeilstöcker
authors.forename: C
authors.initials: C
authors.lastname: Zielinski
authors.forename: J
authors.initials: J
authors.lastname: Drach
mesh_terms: D000368:Aged; D001853:Bone Marrow; D002882:Chromosomes, Human, Pair 13; D018450:Disease Progression; D017353:Gene Deletion; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D010265:Paraproteinemias / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains