Unstable triplet repeat sequences: A source of cancer mutations?
Article first published online: 1 JAN 1996
Copyright © 1995 AlphaMed Press
Volume 13, Issue 2, pages 146–157, 1995
How to Cite
Panzer, S., Kuhl, D. P. A. and Caskey, C. T. (1995), Unstable triplet repeat sequences: A source of cancer mutations?. STEM CELLS, 13: 146–157. doi: 10.1002/stem.5530130206
- Issue published online: 23 DEC 2008
- Article first published online: 1 JAN 1996
- Manuscript Received: 11 JUL 1994
- Manuscript Accepted: 11 JUL 1994
- Triplet short tandem repeats;
- Tumor suppressor genes;
Numerous mutations have been related to various types of cancer. Short tandem repeats (STRs) are repetitive DNA elements that are often polymorphic in normal populations. Triplet repeat expansion has been related pathogenetically to six diseases: fragile × syndrome, fragile × E syndrome, spinobulbar muscular atrophy, myotonic dystrophy, Huntington's disease, and spinocerebellar ataxia type 1. The characteristics of the GC-rich repeat expansion are diverse and result in profound changes in phenotype, sometimes within a single generation in affected families. We expect that simple repeat expansion will cause some cancers based on our knowledge of these unstable DNA sequences in the previously mentioned genes. This may occur by alteration of tumor suppressor gene expression, alteration in coding features of proteins, or change in bystander oncogene expression such as that which occurs with DNA methylation. The demonstrated meiotic instability could link this mechanism of mutation to familial cancer syndromes. The recent discovery of STR instability at multiple sites in hereditary nonpolyposis colon cancer suggests sequence instability may be a factor in cancer progression. Continued identification of candidate genes containing triplet repeats should allow a ready testing of the hypothesis that unstable simple repeat sequences can cause cancer.