Mismatch Repair Genes and Cancer

ARTICLE SUMMARY The research article ed by Conde and colleagues described the results of an investigation involving several genes that were highly associated with cancer. The class of genes that the investigators studied was the mismatch repair (MMR) genes, which are known to play a role in the repair of any changes in the deoxyribonucleic acid (DNA) sequence (Conde 344). Any change in a single sequence in the DNA is called a mutation and this change may result in the production of a wrong protein. The MMR genes are thus important in every cell because it maintains the normal composition of genes in order for a cell to be fully functional.
The study attempted to screen for two major types of mutations. One type of mutation that was tested for was the loss of heterozygosity, which is a type of mutation that generates a change in the type of genetic transmission of cells. The other type of mutation that was screened in the study was microsatellite instability. This mutation is usually observed in long sequences that were composed of repeating segments. These two types of mutations were considered to be important in determining whether a certain gene does influence the development of cancer.
The study was conducted in a Portugese hospital, wherein approximately 287 patient subjects participants. These patients were already diagnosed to have breast cancer. In addition, there were 547 individuals who also participated in the study as controls, or individuals who were pre-determined to be normal and healthy. The study wanted to estimate the chances of developing breast cancer based on the presence and number of mutations in the MMR genes that were studied.
The MMR genes tested in the investigation included the mismatch repair genes of the MSH family, as well as that of the MLH family. The PMS1 and MUTYH were also other genes that belonged to the MMR class of repair genes. Mutations were determined through genotyping, which basically involved preparing copies of the DNA segments that were involved in generating the aforementioned genes. The preparation involved the use of the polymerase chain reaction, which was an enzymatic test that involved high temperatures and bacterial enzymes that would copy a DNA segment in a test tube. Once enough copies of the DNA segment of interest were produced, these were then subjected to DNA sequencing. This technique allows a researcher to generate the actual DNA sequence that would further used for analysis.
The study showed that mutations in the MLH3 gene were often associated with a lower risk of developing breast cancer. The actual changes in the gene were found to generate a change in the amino acid product, such a proline instead of the expected leucine amino acid. Another mutation in the MLH3 gene involved a mutation that did not affect the amino acid, because praline was still produced, as expected. This type of mutation is known as a synonymous mutation.
The research article is highly technical to read yet it presents very important information that could be used by scientists in solving the health problem of cancer. It is essential that the actual genes involved in breast cancer be identified, so that there would be a method to determine whether an individual is likely to develop cancer in his or her lifetime. The study thus provides very useful information that could help researchers design their future studies. The study was also employed statistical tests that would determine the validity of the results of the investigation. It would be interesting to determine in the near future whether additional genes have also been identified in other forms of cancer. It may be possible that the MMR genes are also associated with the development of other cancers such as that of the lung, prostate and cervix.
Work cited
Conde, J., Susana N. Silva, Ana P. Azevedo, Valdemar Teixeira, Julieta Esperana Pina, Jos Rueff and Jorge F. Gaspar. "Association of Common Variants in Mismatch Repair Genes and Breast Cancer Susceptibility: A Multigene Study." BMC Cancer 9 (2009): 344-352.