title: Lack of somatic hypermutation of IG V(H) genes in lymphoid malignancies with t(2;14)(p13;q32) translocation involving the BCL11A gene.
abstract: The t(2;14)(p13;q32.3) involving the BCL11A and IGH genes is a rare but recurrent chromosomal aberration in B-cell malignancies. Hitherto, juxtaposition of BCL11A and IGH has only been described in B-cell chronic lymphocytic leukemia (B-CLL) and immunocytoma. As subgroups of B-CLL can be distinguished by the pattern of somatic mutation of immunoglobulin variable (V) genes we investigated four lymphomas with IGH/BCL11A involvement for IGH hypermutation. Clonal V(H) gene rearrangements were amplified; in all four cases, sequencing of the amplificates revealed the rearranged V(H) genes to lack somatic mutations. These results suggest that t(2;14)(p13;q32.3) is associated with a subset of B-CLL/immunocytoma characterized by non-mutated IG genes deriving from pre-germinal center B cells. As the translocations in both informative cases are targeted to the switch regions of the IGG2 gene, which is mainly used in T cell-independent immune responses, these translocations presumably occurred in activated B cells in the course of T cell-independent immune responses outside the germinal center.
authors: Institute for Genetics, Department of Internal Medicine I, LFI E4 R706, University of Cologne, Joseph-Stelzmannstrasse 9, D-50931 Cologne, Germany.
authors: R
authors: R
authors: Küppers
authors: T
authors: T
authors: Sonoki
authors: E
authors: E
authors: Satterwhite
authors: S
authors: S
authors: Gesk
authors: L
authors: L
authors: Harder
authors: D G
authors: DG
authors: Oscier
authors: P W
authors: PW
authors: Tucker
authors: M J S
authors: MJ
authors: Dyer
authors: R
authors: R
authors: Siebert
mesh_terms: D002352:Carrier Proteins; D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins