Document Detail


Lack of Bcl-2 expression in follicular lymphoma may be caused by mutations in the BCL2 gene or by absence of the t(14;18) translocation.
MedLine Citation:
PMID:  15682435     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Follicular lymphoma (FL), except grade 3B, is characterized by the chromosomal translocation t(14;18)(q32;q21), which results in over-expression of the Bcl-2 protein. Ten per-cent of all FLs, however, do not show Bcl-2 protein expression with standard immunohistochemistry using a monoclonal Bcl-2 antibody against residues 41-54 of the Bcl-2 protein. In this study, the biological background of 18 Bcl-2-negative FL cases grade I, II, or IIIa was investigated by immunohistochemical staining and western blot analysis with alternative antibodies. Bcl-2 protein was demonstrated in five of the 18 cases and all of these carried the t(14;18) translocation. Of the 13 cases that were Bcl-2 negative with alternative antibodies, 12 lacked the t(14;18) translocation. PCR and subsequent sequence analysis of cDNA demonstrated that three cases with a t(14;18) contained somatic mutations in the translocated BCL2 gene, resulting in amino acid replacements in the region of the epitope recognized by the antibody. In conclusion, the majority of Bcl-2-negative FL lack a t(14;18) but a significant subset of these tumours are false negative due to mutations in the BCL2 gene. These findings may have consequences for the use of Bcl-2 immunohistochemistry for diagnostic purposes.
Authors:
Margit Schraders; Daphne de Jong; Philip Kluin; Patricia Groenen; Han van Krieken
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pathology     Volume:  205     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-03     Completed Date:  2005-03-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  329-35     Citation Subset:  IM    
Affiliation:
Department of Pathology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. m.schraders@pathol.umcn.nl
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Chromosomes, Human, Pair 14 / genetics
Chromosomes, Human, Pair 18 / genetics
False Negative Reactions
Genes, bcl-2*
Humans
In Situ Hybridization, Fluorescence
Lymphoma, Follicular / genetics*,  metabolism
Mutation*
Neoplasm Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Sequence Analysis, DNA / methods
Translocation, Genetic
Tumor Markers, Biological / metabolism*
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Markers, Biological

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