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Title: Telomere instability detected in sporadic colon cancers, some showing mutations in a mismatch repair gene.
Authors: Pickett, HA
Baird, DM
Hoff-Olsen, P
Meling, GI
Rognum, TO
Shaw, J
West, KP
Royle, NJ
First Published: 22-Apr-2004
Citation: ONCOGENE, 2004, 23 (19), pp. 3434-3443
Abstract: Human telomeres are essential for genome stability and are composed of long simple tandem repeat arrays (STRs), comprising the consensus TTAGGG repeat interspersed, at the proximal end, with sequence-variant repeats. While the dynamics of telomere attrition through incomplete replication has been studied extensively, the effects on telomeres of error-prone DNA repair processes, known to affect other STRs, are poorly understood. We have compared the TTAGGG and sequence-variant interspersion patterns in the proximal 720 bp of telomeres in colon cancer and normal DNA samples. The frequency of telomere mutations was 5.8% per allele in a randomly collected panel of sporadic colon cancers, showing that telomere mutations occur in vivo. The mutation frequency rose to 18.6% per allele in sporadic tumours that exhibit instability at the polyA tract in the TGFbetaRII gene and to 35% per allele in tumours with somatic mutations in the hMSH2 gene. The majority of the characterized mutations resulted in the loss of one or a few repeats. If the mutation spectrum and frequency described here is reiterated in the rest of the array, there is the potential for extensive telomere destabilization especially in mismatch repair-defective cells. This may in turn lead to a greater requirement for telomere length maintenance earlier in tumourigenesis.
DOI Link: 10.1038/sj.onc.1207477
ISSN: 0950-9232
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Genetics

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