Τρίτη, 10 Νοεμβρίου 2015

ANOTHER GENE FOR COWDEN SYNDROME

Cleveland Clinic researchers have discovered a gene associated with Cowden syndrome, an inherited condition that carries high risks of thyroid, breast, and other cancers, and a subset of noninherited thyroid cancers. These findings were published by Yehia et al in the American Journal of Human Genetics.
Thyroid cancer is the fastest rising cancer in women and second fastest rising in men in the United States. The newly identified gene, SEC23B, discovered by Charis Eng, MD, PhD, Founding Chair of the Genomic Medicine Institute within Cleveland Clinic's Lerner Research Institute and Director of the Center for Personalized Genetic Healthcare, encodes a protein involved in the transport of all proteins within cells.
Analysis Findings
Dr. Eng and her team started their gene-hunting journey 3 years ago by examining a multigenerational family with early-onset thyroid cancers. They found that all affected family members had inherited a harmful mutation in this gene. The mutation was not found in any unaffected family members.
“This isn't the first time we discovered novel genetic mutations in Cowden syndrome,” said Dr. Eng, “but what was truly remarkable is that the SEC23B gene had been identified back in 2009 as the cause of a very rare type of anemia, but not cancer.”
In contrast to anemia, where SEC23B function is lost, Dr. Eng and her team discovered that normal thyroid cells expressing mutated SEC23B grew faster, formed larger colonies, invaded more aggressively, and were able to survive in a very stressful microenvironment—all major hallmarks of cancer.
“Our data not only identified a novel cancer-predisposing gene, particularly in thyroid cancer, but also highlighted how cellular stress responses can be hijacked by cancer cells to promote their survival,” said Dr. Eng.
Further analyses uncovered the findings that SEC23B mutations are present in up to 3% of unrelated Cowden syndrome patients and in 4% of patients with nonsyndromic thyroid cancer. With up to 50% of Cowden syndrome patients testing negative for all known genetic mutations, the syndrome remains an underdiagnosed and difficult-to-recognize condition.
“The discovery of this new cancer-predisposing gene will facilitate predictive genetic testing, risk assessment, genetic counseling, and clinical management of the disease,” said Dr. Eng.
Patients with Cowden syndrome develop noncancerous growths called hamartomas, which can appear on the skin, in mucous membranes, and in the intestinal tract. Cowden syndrome predisposes individuals to several types of cancers—an 85% lifetime risk of breast cancer, a 35% risk for epithelial thyroid cancer, and increased risks of uterine, kidney, and colon cancers. The disease affects one in 200,000 people.
Dr. Eng previously discovered that Cowden syndrome is caused by a faulty tumor-suppressor gene called PTEN (phosphatase and tensin homolog). The gene has since been implicated in a number of other conditions, including a rare form of autism.

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