Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell

Mol Cell. 1999 Jan;3(1):119-23. doi: 10.1016/s1097-2765(00)80180-x.

Abstract

Oncogenes are often dysregulated in B cell tumors as a result of a reciprocal translocation involving an immunoglobulin locus. The translocations are caused by errors in two developmentally regulated DNA recombination processes: V(D)J and IgH switch recombination. Both processes share the property of joining discontinuous sequences from one chromosome and releasing intervening sequences as circles that are lost from progeny cells. Here we show that these intervening sequences may instead insert in the genome and that during productive IgH mu-epsilon switch recombination in U266 myeloma tumor cells, a portion of the excised IgH switch intervening sequences containing the 3' alpha-1 enhancer has inserted on chromosome 11q13, resulting in overexpression of the adjacent cyclin D1 oncogene.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 14 / genetics
  • Cyclin D1 / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Switch Region / genetics*
  • In Situ Hybridization, Fluorescence
  • Molecular Sequence Data
  • Multiple Myeloma / genetics*
  • Oncogenes / genetics
  • Recombination, Genetic / genetics
  • Sequence Alignment
  • Translocation, Genetic / genetics
  • Tumor Cells, Cultured

Substances

  • Immunoglobulin Heavy Chains
  • Cyclin D1

Associated data

  • GENBANK/AF109212
  • GENBANK/AF109213