November 02, 2015
2 min read

Researchers identify new cancer-predisposing gene associated with Cowden disease

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Researchers have discovered a new gene, SEC23B, associated with Cowden disease, an inherited disorder that increases risk for thyroid, breast, endometrial and other cancers.

Cowden disease is a difficult-to-recognize and underdiagnosed autosomal-dominant disorder that has a known association with risk for several cancers.

Charis Eng, MD, PhD

Charis Eng

“More than half of the patients with Cowden syndrome do not have mutations in the known genes,”  Charis Eng, MD, PhD, founding chair of the Genomic Medicine Institute at Cleveland Clinic, director of the center for personalized genetic healthcare at Cleveland Clinic Lerner Research Institute and HemOnc Today Editorial Board member, said in an interview. “This means that molecular diagnosis, gene-informed medical management and predictive testing are not possible. Finding [the new gene] as a novel predisposition gene for Cowden syndrome will enable molecular diagnosis, gene-informed medical management and predictive testing.”

Approximately 1 in 200,000 people are affected by Cowden disease and those who have the disorder have about an 85% lifetime risk for breast cancer and a 35% lifetime risk for epithelial thyroid cancer. Cowden disease is also associated with elevated risks for uterine, kidney and colon cancers.

Using whole-exome and Sanger sequencing of a multi-generational family with a history of early-onset thyroid cancer, Cowden disease and other malignanices, Eng and colleagues discovered the new gene — SEC23B.

“We were fortunate to find a family with Cowden syndrome and early-onset thyroid cancers without mutations in the known predisposition genes,” Eng told HemOnc Today. “We then utilized next generation platforms to finally identify SEC23B.”

Researchers found that all members of the family affected by Cowden disease had inherited a specific mutation of this gene, whereas unaffected family members had a wild-type version of the gene.

“This isn’t the first time we discovered novel genetic mutations in Cowden syndrome,” Eng said in a press release. “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.”

The investigators found that normal thyroid cells harboring mutated SEC23B grow faster, formed larger colonies, invaded aggressively and survived in their microenvironment — all primary indicators of cancer. In the subtype of anemia associated with this mutation, the SEC23B function is lost.

“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,” Eng said in the release.

Further, the researchers found that SEC23B mutations occur in approximately 3% of patients with Cowden disease that is not inherited and in about 4% of patients who have non-syndromic thyroid cancer.

Previously, Eng and colleagues discovered that Cowden disease is caused by PTEN, a faulty tumor suppressor gene that has since been identified as a predictor for other conditions.

“We'd like others to independently validate our findings before translating them to the routine clinical armamentarium,” Eng said. “We will also proceed with studies trying to understand the mechanism of being addicted to ER stress to ensure survival and proliferation.” – by Anthony SanFilippo

For more information:

Charis Eng, MD, PhD, can be reached at

Disclosure: The researchers report no relevant financial disclosures.