Document Detail


Role for CCG-trinucleotide repeats in the pathogenesis of chronic lymphocytic leukemia.
MedLine Citation:
PMID:  11154230     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromosome 11q deletions are frequently observed in chronic lymphocytic leukemia (CLL) in association with progressive disease and a poor prognosis. A minimal region of deletion has been assigned to 11q22-q23. Trinucleotide repeats have been associated with anticipation in disease, and evidence of anticipation has been observed in various malignancies including CLL. Loss of heterozygosity at 11q22-23 is common in a wide range of cancers, suggesting this is an unstable area prone to chromosome breakage. The location of 8 CCG-trinucleotide repeats on 11q was determined by Southern blot analysis of a 40-Mb YAC and PAC contig spanning 11q22-qter. Deletion breakpoints in CLL are found to co-localize at specific sites on 11q where CCG repeats are located. In addition, a CCG repeat has been identified within the minimal region of deletion. Specific alleles of this repeat are associated with worse prognosis. Folate-sensitive fragile sites are regions of late replication and are characterized by CCG repeats. The mechanism for chromosome deletion at 11q could be explained by a delay in replication. Described here is an association between CCG repeats and chromosome loss suggesting that in vivo "fragile sites" exist on 11q and that the instability of CCG repeats may play an important role in the pathogenesis of CLL.
Authors:
R L Auer; C Jones; R A Mullenbach; D Syndercombe-Court; D W Milligan; C D Fegan; F E Cotter
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  97     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-29     Completed Date:  2001-03-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  509-15     Citation Subset:  AIM; IM    
Affiliation:
Department of Experimental Haematology, St Bartholomew's, and The Royal London School of Medicine and Dentistry, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
B-Lymphocytes / ultrastructure
Chromosome Deletion
Chromosomes, Human, Pair 11 / genetics
Contig Mapping
Cytogenetics
Genes, Tumor Suppressor
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / etiology,  genetics*
Lymphoma, Non-Hodgkin / genetics
Trinucleotide Repeats / genetics,  physiology*

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