Scientists identify new gene associated with lung cancer

October 15, 2007

WINSTON-SALEM, N.C. - The first research to show the involvement of a gene known as Dmp1 in human lung cancer will hopefully lead to an increased understanding on what goes wrong at the cellular level to cause the disease, according to researchers from Wake Forest University School of Medicine reporting in Cancer Cell.

The research team found that the Dmp1 gene - which normally works to suppress tumor formation - is non-functional in about 35 percent of human lung cancers.

"Lung cancer is one of the most lethal types of cancer and understanding more about its cause could be a first step to developing new treatments," said senior scientist Kazushi Inoue, M.D., Ph.D., an assistant professor of pathology.

Earlier studies in mice found that the gene is involved in activating tumor suppressors known as p53 and Arf. The researchers believe that when the Dmp1 gene isn't functional, these tumor suppressors are not available to stop tumor growth by killing cancer cells.

"No one thought it was also involved in human tumors," said Inoue. "This was the first study to explore its involvement in human cancer."

The researchers found that deletion of one copy of Dmp1 was found in 30-40 percent of mice lung tumors as well as in human non-small-cell lung cancers. As with all human genes, there are two copies of Dmp1 - one from each parent. Even with one deleted copy, the effects of the gene are silenced, said Inoue.

The research team analyzed 51 samples of human non-small-cell-lung cancers for Dmp1, Arf and p53 and found that the Dmp1 gene was frequently deleted. In most cases, the genes for Arf and p53 tumor suppressors were present, but the suppressors were not active. Even when just one copy of the Dmp1 gene was deleted, the function of Dmp1 was significantly decreased.

The Dmp1 gene is located on human chromosome 7q21, a region that is often deleted in human malignancies. In addition, abnormality of the p53 gene is one of the most common events in human lung cancers.

"This work provides evidence that Dmp1 is a physiological regulator of the Arf-p53 pathway in humans and is primarily involved in lung cancer," said Inoue.

He said that while the research is early basic science, it represents several opportunities to understand more about lung cancer.

"We hope to learn how the gene affects outcome," said Inoue. "It's possible that knowing which patients have the gene may be a prognostic factor for how they will respond to chemotherapy. The gene may also be a target for future drug development since high expression of Dmp1 significantly inhibited the growth of some lung cancer cells."

The study was conducted with the Center for Human Genomics at Wake Forest.

Lung cancer is the leading cause of cancer deaths in the world and accounts for more solid tumor deaths than any other cancers. More than 170,000 new cases are diagnosed each year in the United States and about 160,000 will eventually die of the disease, representing 30 percent of all cancer deaths.
Co-researchers were Ali Mallakin, Ph.D., the lead author, Takayuki Sugiyama, M.D., Pankaj Taneja, Ph.D., Lauren A. Matise, B.S., Donna P. Frazier, Ph.D., Mayur Choudhary, B.S., Gregory A. Hawkins, Ph.D., Ralph B. D'Agostino Jr., Ph.D., and Mark C. Willingham, M.D., all with Wake Forest.

Media Contacts: Karen Richardson,; Shannon Koontz,; at 336-716-4587.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in primary care and 44th in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

Wake Forest Baptist Medical Center

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