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

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.
AuthorsT Goossens, U Klein, R Küppers
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 5 Pg. 2463-8 (Mar 03 1998) ISSN: 0027-8424 [Print] United States
PMID9482908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
Topics
  • B-Lymphocytes (immunology)
  • Base Sequence
  • Flow Cytometry
  • Gene Deletion
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin
  • Heavy Chain Disease (genetics, 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

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