Telomere instability detected in sporadic colon cancers, some showing mutations in a mismatch repair gene

Pickett, Hilda Amelia, Baird, Duncan Martin ORCID: https://orcid.org/0000-0001-8408-5467, Hoff-Olsen, Per, Meling, Gunn Iren, Rognum, Torleiv Ole, Shaw, Jacqui, West, Kevin Paul and Royle, Nicola Jane 2004. Telomere instability detected in sporadic colon cancers, some showing mutations in a mismatch repair gene. Oncogene 23 (19) , pp. 3434-3443. 10.1038/sj.onc.1207477

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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 TGFbRII 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	telomere; mutation; microsatellite instability; mismatch repair; colon cancer
Publisher:	Nature Publishing
ISSN:	0950-9232
Last Modified:	21 Oct 2022 09:53
URI:	https://orca.cardiff.ac.uk/id/eprint/38167

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