Document Detail

Nonreciprocal chromosomal translocations in renal cancer involve multiple DSBs and NHEJ associated with breakpoint inversion but not necessarily with transcription.
MedLine Citation:
PMID:  23341332     Owner:  NLM     Status:  MEDLINE    
Chromosomal translocations and other abnormalities are central to the initiation of cancer in all cell types. Understanding the mechanism is therefore important to evaluate the evolution of cancer from the cancer initiating events to overt disease. Recent work has concentrated on model systems to develop an understanding of the molecular mechanisms of translocations but naturally occurring events are more ideal case studies since biological selection is absent from model systems. In solid tumours, nonreciprocal translocations are most commonly found, and accordingly we have investigated the recurrent nonreciprocal t(3;5) chromosomal translocations in renal carcinoma to better understand the mechanism of these naturally occurring translocations in cancer. Unexpectedly, the junctions of these translocations can be associated with site-specific, intrachromosomal inversion involving at least two double strand breaks (DSB) in cis and rejoining by nonhomologous end joining or micro-homology end joining. However, these translocations are not necessarily associated with transcribed regions questioning accessibility per se in controlling these events. In addition, intrachromosomal deletions also occur. We conclude these naturally occurring, nonreciprocal t(3;5) chromosomal translocations occur after complex and multiple unresolved intrachromosomal DSBs leading to aberrant joining with concurrent interstitial inversion and that clonal selection of cells is the critical element in cancer development emerging from a plethora of DSBs that may not always be pathogenic.
Hanif Ali; Angelika Daser; Paul Dear; Henry Wood; Pamela Rabbitts; Terence Rabbitts
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-23
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  52     ISSN:  1098-2264     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-13     Completed Date:  2013-08-20     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  402-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Base Sequence
Cell Line, Tumor
Chromosome Breakpoints
Chromosome Inversion
Chromosomes, Human, Pair 3 / genetics
Chromosomes, Human, Pair 5 / genetics
DNA Breaks, Double-Stranded*
DNA Copy Number Variations
DNA End-Joining Repair*
Kidney Neoplasms / genetics,  pathology
Molecular Sequence Data
Transcription, Genetic*
Translocation, Genetic*
Grant Support
G0600914//Medical Research Council; //Medical Research Council

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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