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PMID: 1495966 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Clonal evolution of a follicular lymphoma: evidence for antigen selection.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 15 ·1992-08-01 ·Pages 6770-4

Bahler DW, Levy R

Abstract

The potential role antigens play in growth stimulation or in clonal selection of follicular lymphomas is unknown. To study this issue, we sequenced the immunoglobulin heavy chain variable region genes expressed by a follicular lymphoma from multiple biopsy specimens and also cloned and sequenced the corresponding germ-line variable gene from this patient. Comparison to the germ-line gene revealed numerous nucleotide substitutions in all of the lymphoma variable gene sequences. Some of the substitutions may have occurred in the nonmalignant precursor B cell that gave rise to this lymphoma because they were shared among all of the variable genes, but many of the mutations accumulated as the malignant clone expanded. The mutations were distributed in such a way that strongly suggested the majority of tumor cells had been positively selected through their antigen receptor. This was especially evident for the mutations that developed late in the clonal evolution of this lymphoma. These findings indicate that antigen stimulation may be involved in the growth of follicular lymphoma tumors.

MeSH Terms
Antigens, Neoplasm/immunology B-Lymphocytes/immunology Base Sequence Cloning, Molecular DNA, Neoplasm/genetics,isolation & purification Genes, Immunoglobulin Genetic Variation Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin Variable Region/genetics Lymph Nodes/immunology Lymphoma, Follicular/genetics,immunology Molecular Sequence Data Oligodeoxyribonucleotides Phenotype Polymerase Chain Reaction Spleen/immunology
Chemicals
Antigens, Neoplasm DNA, Neoplasm Immunoglobulin Heavy Chains Immunoglobulin Variable Region Oligodeoxyribonucleotides
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Bahler D W
Department of Medicine, Stanford University Medical Center, CA 94305.
Levy 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.89.15.6770
Published
1992-08-01
Pages
6770-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49585
Subset
IM
Grants
NCI NIH HHS · CA33399 · United States
NCI NIH HHS · CA34233 · United States
Databases
GENBANK
M94768
External Links
PubMed source DOI: 10.1073/pnas.89.15.6770 PMC Full Text View journal details
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