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New Colorectal Cancer Gene Identified

Date:
September 27, 2000
Source:
Mayo Clinic
Summary:
Researchers at Mayo Clinic have discovered that mutations in a newly isolated gene, AXIN2, lead to the development of colorectal cancer. This gene belongs to an important cell pathway that contains several other genes whose mutations have also been linked to colorectal or other cancers.

ROCHESTER, Minn. -- Researchers at Mayo Clinic have discovered that mutations in a newly isolated gene, AXIN2, lead to the development of colorectal cancer. This gene belongs to an important cell pathway that contains several other genes whose mutations have also been linked to colorectal or other cancers.

The study, to be published in the Oct. 1 issue of Nature Genetics, demonstrates that mutations in the AXIN2 gene cause colorectal cancer by elevating the level of Beta-catenin, a protein known to be associated with the development of colorectal cancer.

"It has been known for a while that mutations in Adenomatous Polyposis Coli (APC) or Beta-catenin genes cause a certain percentage of colorectal cancer," says Dr. Wanguo Liu, a Mayo Clinic molecular geneticist and lead investigator of this study. "Since AXIN2 interacts with APC and Beta-catenin in the same pathway, we suspected that AXIN2 mutations might also lead to colorectal cancer. We have now confirmed this association to be true."

Dr. Liu and his team of researchers began the current work about two years ago, with the support of three other Mayo Clinic investigators, including Drs. Patrick Roche, David Smith and Stephen Thibodeau. To screen for mutations in the AXIN2 gene, they examined DNA from 105 colorectal cancer samples. Of these samples, 45 had defective mismatch repair, one of the cell’s mechanisms to correct DNA replication errors. All 11 mutations identified were in this group. Thus, the researchers concluded that the AXIN2 mutations appear to be specifically associated with colorectal cancer with defective mismatch repair.

Colorectal cancer accounts for 10 percent of all cancers in the United States. Approximately 130,200 new cases of colorectal cancer will be diagnosed this year and 56,300 people will die from the disease. Previous studies have shown that about 15 percent of all colorectal cancers are associated with defective mismatch repair. Of those with defective mismatch repair, 30 percent now have been shown to harbor mutations in the AXIN2 gene.

According to Dr. Liu, although only a small percentage of colorectal cancer patients could benefit from this finding, the discovery of how defective mismatch repair contributes to colorectal cancer development through mutations in the AXIN2 gene may have broad applications in solving research mysteries in other gastroenterological cancers.

"Clinically, screening for mutations in the AXIN2 gene may aid in distinguishing a subgroup of colorectal cancer from others for specific therapeutic decision-making," says Dr. Liu. "It even may be possible to treat cancers in which the AXIN2 gene is defective by using gene therapy to transplant functional copies of the gene into patients’ cells, thus repairing the genetic defect causing the cancer."

Dr. Liu’s group now has developed a rapid procedure for scanning and detecting mutations in the AXIN2 gene. At present, his team is trying to determine the precise mechanism of how this gene is involved in cancer development and whether this gene product can be used as an effective therapeutic molecule for suppressing growth of colorectal or other cancers.


Story Source:

The above story is based on materials provided by Mayo Clinic. Note: Materials may be edited for content and length.


Cite This Page:

Mayo Clinic. "New Colorectal Cancer Gene Identified." ScienceDaily. ScienceDaily, 27 September 2000. <www.sciencedaily.com/releases/2000/09/000927073816.htm>.
Mayo Clinic. (2000, September 27). New Colorectal Cancer Gene Identified. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2000/09/000927073816.htm
Mayo Clinic. "New Colorectal Cancer Gene Identified." ScienceDaily. www.sciencedaily.com/releases/2000/09/000927073816.htm (accessed August 1, 2014).

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