Researchers pinpoint how one cancer gene functions

February 2, 2011

For several decades, researchers have been linking genetic mutations to diseases ranging from cancer to developmental abnormalities. What hasn't been clear, however, is how the body's genome sustains such destructive glitches in the first place. Now a team of Mayo Clinic scientists and collaborators provide an unprecedented glimpse of a little-understood gene, called MMSET, revealing how it enables disease-causing mutations to occur. The findings appear in the current issue of Nature.

"MMSET had been known for many years, and had been shown to be mutated in several diseases, but its function had never quite been pinpointed," says lead author Zhenkun Lou, Ph.D., Mayo Clinic pharmacologist and senior author of the study.

The researchers found that normally-functioning MMSET is usually helpful. It plays a restorative role within the genome, recruiting proteins like p53-binding protein 1 to repair breaks that occur in DNA and to maintain genetic stability. But when MMSET malfunctions, the protective pathway falls short, and a cascade of mutations take place that can lead to disease processes.

"It was not clear before the study how p53-binding protein 1 was targeted to sites of . We found MMSET regulates this critical pathway," Dr. Lou says. "But when the gene is impaired, cells don't have the correct response to DNA damage." Misregulation of MMSET has been implicated in cancers like the plasma cell cancer as well as the inherited disorder of severe retardation known as Wolf-Hirschhorn syndrome, even though the MMSET mutation looks different in the two diseases.

While the study answers a long baffling mystery about the function of the gene, it also suggests avenues for new therapeutic approaches for several disorders, notes Dr. Lou. One possible route for clinical investigation is for patients with MMSET mutations, which keep DNA from undergoing efficient repair, to be given treatment that will help minimize . For instance, patients with defects in DNA damage-maintenance machinery often succumb to neurological disorders (e.g., ataxia telangiectasia and Wolf-Hirschhorn syndrome), since neurons are very sensitive to DNA damage spontaneously occurring in cells. These patients could be given anti-oxidative treatment to help maintain the health of DNA and preserve neurons.

The finding also suggests new thinking about treating certain cancers. MMSET protein has been found in abundance in hard-to-treat malignancies such as multiple myeloma and glioblastoma, a devastating brain tumor.

"It may be that these cancers don't respond well to chemotherapy treatment, which works by interrupting DNA, because the [MMSET producing] cancer cells are more efficient at repairing themselves," Dr. Lou says. Dr. Lou is currently working with the National Institutes of Health-Mayo Brain Tumor SPORE (Specialized Program of Research Excellence) to investigate whether MMSET levels will be a biomarker to guide glioblastoma treatment. Future investigations may involve inhibiting MMSET in proliferating cancer cells, which may make cancers more responsive to cell-killing chemotherapies.

Related Stories

Recommended for you

New approach to studying chromosomes' centers may reveal link to Down syndrome and more

November 20, 2017
Some scientists call it the "final frontier" of our DNA—even though it lies at the center of every X-shaped chromosome in nearly every one of our cells.

Genome editing enhances T-cells for cancer immunotherapy

November 20, 2017
Researchers at Cardiff University have found a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers.

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.