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Publication : Telomere loss as a mechanism for chromosome instability in human cancer.

First Author  Murnane JP Year  2010
Journal  Cancer Res Volume  70
Issue  11 Pages  4255-9
PubMed ID  20484032 Mgi Jnum  J:160686
Mgi Id  MGI:4454943 Doi  10.1158/0008-5472.CAN-09-4357
Citation  Murnane JP (2010) Telomere loss as a mechanism for chromosome instability in human cancer. Cancer Res 70(11):4255-9
abstractText  Cancer cells commonly have a high rate of telomere loss, even when expressing telomerase, contributing to chromosome instability and tumor cell progression. This review addresses the hypothesis that this high rate of telomere loss results from a combination of four factors. The first factor is an increase in the frequency of double-strand breaks (DSB) at fragile sites in cancer cells due to replication stress. The second factor is that telomeres are fragile sites. The third factor is that subtelomeric regions are highly sensitive to DSBs, so that DSBs near telomeres have an increased probability of resulting in chromosome instability. The fourth factor is that cancer cells may be deficient in chromosome healing, the de novo addition of telomeres to the sites of DSBs, a mechanism that prevents chromosome instability resulting from DSBs near telomeres. Understanding these factors and how they influence telomere loss will provide important insights into the mechanisms of chromosome instability and the development of novel approaches for anti-cancer therapy. Cancer Res; 70(11); 4255-9. (c)2010 AACR.
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