title: Loss of 1p and rearrangement of MYC are associated with progression of smouldering myeloma to myeloma: sequential analysis of a single case.
abstract: We report serial genetic studies on a young female patient initially diagnosed with asymptomatic smouldering myeloma who progressed to symptomatic myeloma 4.5 years after presentation. An unbalanced translocation, der(14)t(4;14)(p16;q32), was initially found in all plasma cells plus deletions of other chromosomal regions as detected by array-based comparative genomic hybridization. Deletion of chromosome 13 was observed in a minor population of plasma cells (<20%) for the first two years, increasing to 100% of plasma cells by the time of multiple myeloma diagnosis. Loss of 1p and a rearrangement of MYC were first observed in a small population of plasma cells one year prior to the clinical diagnosis of multiple myeloma, but these subclones increased rapidly in size to become the major population suggesting that they were directly involved in the transformation process. This case report provides a unique insight into the mechanisms of disease progression from smouldering multiple myeloma to multiple myeloma.
authors.affiliation: Leukaemia Research Fund UK Myeloma Forum Cytogenetics Group, Human Genetics Division, University of Southampton, Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wilts, UK. laura.chiecchio@salisbury.nhs.uk
authors.forename: Laura
authors.initials: L
authors.lastname: Chiecchio
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Dagrada
authors.forename: Rebecca K M
authors.initials: RK
authors.lastname: Protheroe
authors.forename: David M
authors.initials: DM
authors.lastname: Stockley
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Smith
authors.forename: Kim H
authors.initials: KH
authors.lastname: Orchard
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000648:ultrastructure*; D055028:Comparative Genomic Hybridization; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008957:Models, Genetic; D009101:Multiple Myeloma / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D013997:Time Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D016271:Proto-Oncogene Proteins c-myc