Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease

Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2463-8. doi: 10.1073/pnas.95.5.2463.

Abstract

Human naive and germinal center (GC) B cells were sorted by flow cytometry and rearranged VH region genes were amplified and sequenced from single cells. Whereas no deletions or insertions were found in naive B cells, approximately 4% of in-frame and >40% of out-of-frame rearrangements of GC B cells harbored deletions and/or insertions of variable length. The pattern of deletions/insertions and their restriction to mutated V genes strongly suggests that they result from somatic hypermutation. Deletions and insertions account for approximately 6% of somatic mutations introduced into rearranged VH region genes of GC B cells. These deletions/insertions seem to be the main cause for the generation of heavy chain disease proteins. Furthermore, it appears that several types of oncogene translocations (like c-myc translocations in Burkitt's lymphoma) occur as a byproduct of somatic hypermutation within the GC-and not during V(D)J recombination in the bone marrow as previously thought.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • Base Sequence
  • Flow Cytometry
  • Gene Deletion*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Genes, Immunoglobulin*
  • Heavy Chain Disease / genetics*
  • Heavy Chain Disease / immunology
  • Hodgkin Disease / genetics
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Lymphoma, Non-Hodgkin / genetics
  • Molecular Sequence Data
  • Multigene Family*
  • Oncogenes*
  • Polymerase Chain Reaction
  • Translocation, Genetic*

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region

Associated data

  • GENBANK/AJ225682
  • GENBANK/AJ225683
  • GENBANK/AJ225684
  • GENBANK/AJ225685
  • GENBANK/AJ225686
  • GENBANK/AJ225687
  • GENBANK/AJ225688
  • GENBANK/AJ225689
  • GENBANK/AJ225690
  • GENBANK/AJ225691
  • GENBANK/AJ225692
  • GENBANK/AJ225693
  • GENBANK/AJ225694
  • GENBANK/AJ225695
  • GENBANK/AJ225696
  • GENBANK/AJ225697
  • GENBANK/AJ225698
  • GENBANK/AJ225699
  • GENBANK/AJ225700
  • GENBANK/AJ225701
  • GENBANK/AJ225702
  • GENBANK/AJ225703
  • GENBANK/AJ225704
  • GENBANK/AJ225705
  • GENBANK/AJ225706
  • GENBANK/AJ225707
  • GENBANK/AJ225708
  • GENBANK/AJ225709
  • GENBANK/AJ225710
  • GENBANK/AJ225711