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

  • Tina Goossens
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany
  • Ulf Klein
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany
  • Ralf Küppers
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany

書誌事項

公開日
1998-03-03
DOI
  • 10.1073/pnas.95.5.2463
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p>Human naive and germinal center (GC) B cells were sorted by flow cytometry and rearranged V<jats:sub>H</jats:sub>region genes were amplified and sequenced from single cells. Whereas no deletions or insertions were found in naive B cells, ≈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 ≈6% of somatic mutations introduced into rearranged V<jats:sub>H</jats:sub>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.</jats:p>

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