title: Molecular characterization of a t(2;7) translocation linking CDK6 to the IGK locus in CD5(-) monoclonal B-cell lymphocytosis.
abstract: The term monoclonal B-cell lymphocytosis (MBL) is used to characterize individuals with a circulating population of clonal B-cells and no other features of a lymphoproliferative disorder. Although several recent studies have examined the molecular basis of this condition, the subgroup of MBL lacking CD5 expression has been largely overlooked. In this study, we sequenced a t(2;7) in a patient with persistent but non-progressing CD5(-) MBL. This revealed a breakpoint at 2p11.2 localized to the recombination signal sequence (RSS) of the immunoglobulin κ (IGK) variable gene IGKV3-15, and a breakpoint at 7q21.2 located 520 base pairs (bp) upstream of the transcription start site of cyclin-dependent kinase 6 (CDK6 ). The 7q breakpoint showed perfect sequence homology to the immunoglobulin RSS heptamer, and was located within 3 bp of a t(2;7) junction previously characterized in splenic marginal zone lymphoma (SMZL). These findings highlight a genetic link between CD5(-) MBL and SMZL, and implicate the dysregulation of CDK6 in the emergence of this preclinical disorder.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Parker
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Macdonald
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000368:Aged; D001402:B-Lymphocytes; D018956:CD5 Antigens / Q000235:genetics; D002889:Chromosomes, Human, Pair 2; D002897:Chromosomes, Human, Pair 7; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics*; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008218:Lymphocytosis / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D018956:CD5 Antigens; D007145:Immunoglobulin kappa-Chains; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6