Document Detail

Extreme variation in apoptosis capacity amongst lymphoid cells of Nijmegen breakage syndrome patients.
MedLine Citation:
PMID:  17977616     Owner:  NLM     Status:  MEDLINE    
The human genetic disorder, Nijmegen breakage syndrome (NBS), is characterised by radiosensitivity, immunodeficiency and an increased risk for cancer, particularly lymphoma. The NBS1 gene codes for a protein, nibrin, involved in the processing/repair of DNA double strand breaks and in cell cycle checkpoints. The majority of patients (>90%) are homozygous for a founder mutation. Despite this genetic homogeneity, the syndrome shows considerable clinical variability, for example, in age at development of a malignancy. We hypothesised that one reason for such variation might be individual differences in the clearance of heavily damaged precancerous cells by apoptosis. To test this hypothesis we have examined a set of 30 lymphoblastoid B-cell lines from NBS patients for their capacity to enter into apoptosis after a DNA-damaging treatment. There was a substantial 40-fold variation in apoptosis between cell lines from different patients. NBS patient cell lines could be grouped into a large, apoptosis-deficient group and a smaller group with essentially normal apoptotic response to DNA damage. In both groups, cell lines were proficient in TP53 phosphorylation and stabilisation after the same DNA-damaging treatment. Thus the observed variation in apoptosis capacity is not due to failure to activate TP53. Despite the large variation in apoptosis, no statistically significant correlation between apoptotic capacity of patient cell lines and clinical course of the disease was apparent.
Nadja Thierfelder; Ilja Demuth; Nadine Burghardt; Karin Schmelz; Karl Sperling; Krystyna H Chrzanowska; Eva Seemanova; Martin Digweed
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-30
Journal Detail:
Title:  European journal of cell biology     Volume:  87     ISSN:  0171-9335     ISO Abbreviation:  Eur. J. Cell Biol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-21     Completed Date:  2008-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906240     Medline TA:  Eur J Cell Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  111-21     Citation Subset:  IM    
Institut für Humangenetik, Charité - Universitätsmedizin Berlin, Germany.
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MeSH Terms
B-Lymphocytes / cytology,  physiology*
Bleomycin / pharmacology
Cell Cycle Proteins / metabolism
Cell Line, Tumor
DNA Damage
Nijmegen Breakage Syndrome / metabolism,  pathology,  physiopathology*
Nuclear Proteins / metabolism
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/Cell Cycle Proteins; 0/NBN protein, human; 0/Nuclear Proteins; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 11056-06-7/Bleomycin

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