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PMID: 9482908 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 5 ·1998-03-03 ·Pages 2463-8

Goossens T, Klein U, Küppers R

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.

MeSH Terms
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
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin Variable Region
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Goossens T
Institute for Genetics, University of Cologne, 50931 Cologne, Germany. [email protected]
Klein U
Küppers R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.5.2463
Email
[email protected]
Published
1998-03-03
Pages
2463-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19376
Subset
IM
Databases
GENBANK
AJ225682, AJ225683, AJ225684, AJ225685, AJ225686, AJ225687, AJ225688, AJ225689, AJ225690, AJ225691, AJ225692, AJ225693, AJ225694, AJ225695, AJ225696, AJ225697, AJ225698, AJ225699, AJ225700, AJ225701, AJ225702, AJ225703, AJ225704, AJ225705, AJ225706, AJ225707, AJ225708, AJ225709, AJ225710, AJ225711
External Links
PubMed source DOI: 10.1073/pnas.95.5.2463 PMC Full Text View journal details
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