title: Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma.
abstract: The ability to rearrange the germ-line DNA to generate antibody diversity is an essential prerequisite for the production of a functional repertoire. While this is essential to prevent infections, it also represents the "Achilles heel" of the B-cell lineage, occasionally leading to malignant transformation of these cells by translocation of protooncogenes into the immunoglobulin (Ig) loci. However, in evolutionary terms this is a small price to pay for a functional immune system. The study of the configuration and rearrangements of the Ig gene loci has contributed extensively to our understanding of the natural history of development of myeloma. In addition to this, the analysis of Ig gene rearrangements in B-cell neoplasms provides information about the clonal origin of the disease, prognosis, as well as providing a clinical useful tool for clonality detection and minimal residual disease monitoring. Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the pathobiology of myeloma.
authors.affiliation: Section of Haemato-Oncology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, UK.
authors.forename: David
authors.initials: D
authors.lastname: González
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: James A
authors.initials: JA
authors.lastname: Fenton
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D015321:Gene Rearrangement / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008954:Models, Biological; D009101:Multiple Myeloma / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D010266:Paraproteins / Q000235:genetics; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C014609:IgK; D007136:Immunoglobulins; D010266:Paraproteins