title: Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis.
abstract: Primary systemic amyloidosis (AL) is a plasma cell (PC) dyscrasia with clinical similarities to multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), but its molecular basis is poorly understood. Translocations at the immunoglobulin heavy-chain (IgH) locus, 14q32, are likely early genetic events in both MM and MGUS and involve several nonrandom, recurrent, partner chromosomes such as 11q13, 16q23, and 4p16.3. Given the similarities between MM, MGUS, and AL, bone marrow clonal PCs were evaluated in 29 patients with AL using interphase fluorescence in situ hybridization (FISH) combined with immunofluorescence detection of the cytoplasmic light-chain (cIg-FISH) for the presence of 14q32 translocations and the t(11;14)(q13;q32). Of 29 patients studied, 21 (72.4%) showed results compatible with the presence of a 14q32 translocation, and 16 (76.2%) of those had translocation (11;14)(q13;q32) for an overall prevalence of the abnormality of 55%. IgH translocations are common in AL, especially the t(11;14)(q13;q32).
authors.affiliation: Departments of Hematology and Internal Medicine and of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Hayman
authors.forename: R J
authors.initials: RJ
authors.lastname: Bailey
authors.forename: S M
authors.initials: SM
authors.lastname: Jalal
authors.forename: G J
authors.initials: GJ
authors.lastname: Ahmann
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
authors.forename: P R
authors.initials: PR
authors.lastname: Greipp
authors.forename: R A
authors.initials: RA
authors.lastname: Kyle
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: S V
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: T E
authors.initials: TE
authors.lastname: Witzig
authors.forename: J A
authors.initials: JA
authors.lastname: Lust
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000235:genetics*; D001854:Bone Marrow Cells / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D015995:Prevalence; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains