Testing the Elephant Man's DNA: An Interview With Dr. Charis Eng

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For years, doctors and scientists have tried to find an accurate diagnosis for the Elephant Man's (Joseph Merrick) illness. Without the assistance of modern DNA testing tools, it has been hard to discover what caused Joseph Merrick's deformities that would later cause people to refer to him as the Elephant Man.

In the late 1970s doctors began to theorize that a disease known as Proteus syndrome could be the cause of the Elephant Man's condition. Proteus syndrome is a rare condition caused by a mutated gene called PTEN.

So researchers in England enlisted the help of Dr. Charis Eng, Director of the Division of Human Genetics at Ohio State University. She is one of the world's leading experts on PTEN. Dr. Eng tested Merrick's DNA in search of a link. We sat down with her to find out more about it:

Q:		Where did you get the idea that Proteus syndrome, one of the diseases Joseph Merrick was afflicted with, could be caused by a mutated PTEN gene?
A:		As a clinician as well as scientist, I noted that the unusual tissue growth of Proteus syndrome was slightly reminiscent of other disorders caused by germline (in every cell of the body) PTEN mutation that we were studying, such as Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome (BBRS).

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Q:		How does the PTEN gene — a tumor suppressor — work?
A:		PTEN acts like a brake to stop the overgrowth of a cell. When PTEN itself is not working (through damage or mutation), a cell can go haywire and multiply at a random rate. Thus, damaged or mutated PTEN leads to a number of different types of cancers.

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Q:		What does PTEN stand for?
A:		Phosphatase and tensin homolog on chromosome 10 (10q23.3).

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Q:		What are the primary goals of your scientific research?
A:		We use DNA to identify and understand genes that are involved in cancer and cancer-related diseases. We do studies that focus on the role of the PTEN gene in causing or activating cancers and other diseases. Our work will lead to further understanding of the machinery of how cells function in health and disease. This knowledge has already led to further diagnostic tests. Understanding the machinery of the cell will also help us develop new preventative and therapeutic agents.

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Q:		Does germline PTEN mutation predispose people to various types of cancer, or other diseases?
A:		Yes, it can. Remember, when an individual inherits an altered cancer-predisposing gene, it does not mean they are 100 percent doomed to developing that cancer. This is the concept of penetrance.

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Q:		If so, what is the frequency, or average likelihood, that they'll develop a certain cancer?
A:		Individuals carrying germline mutations in PTEN are predisposed to breast cancer (up to 50 percent lifetime risk in women); thyroid cancer (10 percent lifetime risk); and endometrial cancer (perhaps 6-10 percent lifetime risk in women). It is believed that other cancers are associated with germline PTEN mutations, but there is little epidemiologic data to back these up.

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Q:		What are gene therapies for those whose PTEN genes have become damaged or mutated?
A:		There are no gene therapies for PTEN-related disorders. In general, gene therapy for cancer does not work and has not worked even after two or more decades of such research. What we clinical cancer geneticists do is to try to identify individuals with germline PTEN mutations even before they develop cancer, so-called predictive testing, so that clinical surveillance and/or prophylactic surgery can be instituted.

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Q:		What other type of research is being conducted related to the PTEN gene?
A:		There are many active research programs targeting PTEN in many labs around the world. Describing each would take more than a book. PTEN is the hottest molecule since p53. I daresay that PTEN has usurped p53's title of "Master Molecule."

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Q:		Could you offer any other elaboration on your work that you feel is important?
A:		We are not only studying PTEN from a genetic point of view, but are dissecting the workings of PTEN from a multidisciplinary approach. In addition to genetic inactivation of PTEN, we are looking into nontraditional mechanisms of PTEN inactivation. This type of bedside-to-bench-to-bedside approach is important so that our patients will quickly benefit from our studies. Dr. Eng is the director of the Clinical Cancer Genetics Program and the Division of Human Genetics as well as professor of medicine at Ohio State University. She is one of the world's leading experts on PTEN.

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