Disobedient gene increases Thyroid cancer risk; finding leads to new treatment
Three renegade genes, one of which no longer performs its tumor-suppressing role in the human body, lead to increased risk of thyroid cancer according to researchers at the Cleveland Clinic in a release issued today. The discovery should help scientists develop specific molecular-targeted cancer treatments depending on which gene is involved.
Studies led by Dr. Charis Eng, chair and founding director of the Genomic Medicine Institute of Cleveland Clinic’s Lerner Research Institute, show that mutations in the Phosphatase and Tensin Homolog (PTEN) gene can cause Cowden syndrome that appears as small, benign tumors on the nose, in the mouth, and elsewhere on the body. Individuals with Cowden syndrome are at greater risk of developing thyroid, breast, and other cancers, Dr. Eng said.
In research that also included studies of the SDH and KLLN genes, Dr. Eng and her team monitored nearly 3,000 patients diagnosed with Cowden syndrome (CS) or CS-like disease and found PTEN gene mutations in 80 percent of those patients. When the gene mutates, it is no longer able to regulate cell survival and division which can lead to the formulation of tumors.
PTEN is a protein in the human body that controls the cell cycle preventing cells from growing or dividing too rapidly. When functioning properly, the gene acts as a chemical pathway signaling to cells when to stop dividing and to begin a “programmed” death cycle. When a mutation occurs, news cells proliferate while old cells live longer. However, until recently, researchers knew nothing about PTEN.
“When I decided to set out to find the gene(s) associated with CS, PTEN was not known,” Dr. Eng related. “By mapping big families with Cowden syndrome, it pointed to a part of chromosome 10 where we found PTEN. After we found PTEN, we realized that when altered, it led to Cowden syndrome and its cancer predisposition. Our’s and others' studies then revealed that PTEN was a tumor suppressor.
“Unfortunately, only a fraction of CS was caused by mutations in PTEN, thus rendering this molecular diagnostic less sensitive. We looked at KLLN (KILLIN) because it was recently found to be right next to PTEN and that they shared a bidirectional promoter,” Dr. Eng continued. “Because of this research over the last 12 years since we uncovered PTEN and CS, there are clinical guidelines on how and when to start close monitoring and early screening for breast, thyroid, endometrial and colon cancers.”
In another aspect of the Dr. Eng’s research, recently mentioned in the Journal of Clinical Endocrinology and Metabolism, mutations in the PTEN gene play an important role in children under the age of 18 suffering from thyroid cancer. Although all three genes, PTEN, SDH, and KLLN, have links to the cancer, only a mutated PTEN had the dubious distinction of causing the disease in children. As a result, researchers recommend that the thyroids of children who experience PTEN-causing CS syndrome receive increased surveillance. The testing for PTEN mutations might also suggest looking for other cancers or maladies in children, scientists said.
Thyroid cancer, according to the Mayo Clinic in Minnesota, occurs in cells of the thyroid – a butterfly-shaped gland located at the base of the neck, just below the Adam’s apple. The gland produces hormones that regulate heart rate, blood pressure, body temperature, and weight. Although thyroid cancer isn’t common in the United States, rates seem to be increasing. Physicians believe this is because new technology allows them to find small thyroid cancers that may not have been found in the past. Most cases of thyroid cancer can be cured with treatment.
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