Frameshift mutations

Cancer

Frameshift mutations are known to be a factor in colorectal cancer as well as other cancers with microsatellite instability. As stated previously, frameshift mutations are more likely to occur in a region of repeat sequence. When DNA mismatch repair does not fix the addition or deletion of bases, these mutations are more likely to be pathogenic. This may be in part because the tumor is not told to stop growing. Experiments in yeast and bacteria help to show characteristics of microsatellites that may contribute to defective DNA mismatch repair. These include the length of the microsatellite, the makeup of the genetic material and how pure the repeats are. Based on experimental results longer microsatellites have a higher rate of frameshift mutations. The flanking DNA can also contribute to frameshift mutations. In prostate cancer a frameshift mutation changes the open reading frame (ORF) and prevents apoptosis from occurring. This leads to an unregulated growth of the tumor. While there are environmental factors that contribute to the progression of prostate cancer, there is also a genetic component. During testing of coding regions to identify mutations, 116 genetic variants were discovered, including 61 frameshift mutations. There are over 500 mutations on chromosome 17 that seem to play a role in the development of breast and ovarian cancer in the BRCA1 gene, many of which are frameshift.