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(Last updated 11/5/03)

Previous stories related to Professor Eng's research:

"Genetic Alteractions In Stromal Breast Tissue May Make Cancer Detection More Difficult," 12/19/02.

"Gene Alterations May Predict Response To New Cancer Therapy," 7/26/99.



Columbus, Ohio – Scientists have linked gene defects to a rare disorder that enlarges part of the brain and may cause seizures and mental retardation. Normally, the gene halts cell division and helps eliminate damaged and potentially cancerous cells.

Charis Eng

The study by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute suggests that mutations in a gene known as PTEN are linked to Lhermitte-Duclos disease (LDD), a rare disorder that may or may not cause symptoms.

The findings also tie LDD to Cowden syndrome, also a poorly recognized disorder, which increases a person’s risk of developing cancers of the breast, thyroid and uterus. The study is published in the November issue of the American Journal of Human Genetics.

“Taken together, the frequency and pattern of mutations suggest that LDD and Cowden syndrome share a common genetic cause,” Eng says, “and that LDD is a manifestation of Cowden syndrome.”

“Our study strongly suggests that a person with LDD probably also has Cowden syndrome, even in the absence of other features or a family history of the syndrome,” says lead investigator Charis Eng, professor of internal medicine and director of Clinical Cancer Genetics within the Human Cancer Genetics Program at the Comprehensive Cancer Center-James.

“Just as with people with Cowden syndrome, we recommend that people with LDD are monitored throughout life for breast, thyroid and endometrial cancer. Family members also should undergo genetic testing because offspring have a fifty-fifty chance of inheriting the mutations.”

The findings of this study may change the diagnostic criteria for Cowden syndrome and lead to a better understanding of the syndrome’s cause and of PTEN’s role in normal and cancerous cells.

Cowden syndrome causes small bumps on the skin that involve hair follicles and small, wart-like skin growths. The syndrome also sometimes causes large head-size and benign fatty tumors. The incidence of Cowden syndrome is thought to be about 1 in 200,000, says Eng, but could be more common.

“Physicians often don’t recognize it,” she says.

LDD is a rare disorder. It causes a non-cancerous enlargement, or overgrowth, of regions of the cerebellum in the brain’s balancing center. Visible symptoms may not arise.

PTEN (for “phosphatase and tensin homologue deleted on chromosome ten”) is a so-called “guardian” gene that stops cell division so that cells can repair damaged DNA. If the damage cannot be repaired, it triggers the process of programmed cell death, or apoptosis, thereby eliminating genetically damaged and potentially cancerous cells.

More than 80 percent of people with Cowden syndrome are born with PTEN mutations, which means the mutation is found in every cell in the body and can be passed on to offspring. PTEN mutations also are found in tumor cells of many spontaneous (i.e., non-inherited) cancers, including thyroid and endometrial cancers and certain brain tumors.

For this study, Eng and her collaborators analyzed DNA extracted from enlarged brain tissue removed from 18 LDD patients. Of the 18 cases, 15 showed PTEN mutations. Each of these 15 patients had developed LDD in adulthood; the three patients without PTEN mutations had developed LDD as children.

“Taken together, the frequency and pattern of mutations suggest that LDD and Cowden syndrome share a common genetic cause,” Eng says, “and that LDD is a manifestation of Cowden syndrome.”

Grants from the American Cancer Society and the National Cancer Institute supported this research. Eng is a recipient of the Doris Duke Distinguished Clinical Scientist Award.


Contact: Darrell E. Ward, (614) 293-3737; Ward-15@medctr.osu.edu