Scientists find new supressor gene involved in breast, prostate and other cancers

March 29, 2001

BETHESDA, MD -- Scientists at the National Human Genome Research Institute (NHGRI) and the M.D. Anderson Cancer Center at the University of Texas have found a novel tumor suppressor gene on human chromosome 7 that appears to be involved in a wide range of cancers. Tumor suppressor genes play a key role in the regulation of cell growth. Scientists have known for about 15 years that when a tumor suppressor gene is inactivated, the cells it affects grow out of control and become cancerous.

"Inactivating a tumor suppressor gene is like disabling the brakes on a car," says the study's corresponding author, Eric Green, M.D., Ph.D., chief of the Genome Technology Branch in the NHGRI Division of Intramural Research. "Without the function of such a gene, a tumor keeps growing out of control. And just like a car without brakes, the consequences can be fatal."

In the new study, published in the April issue of Nature Genetics, the researchers reported finding the new gene, which they named ST7, short for Suppression of Tumorigenicity 7, on chromosome 7. Studies show that the gene is widely expressed in normal tissues throughout the body and that the gene is often disrupted by mutation or deletion in tumors arising from epithelial cells, such as cancers of the breast, prostate, colon and ovary.

Scientists know of at least 30 tumor suppressor genes and a search of gene databases suggests that there may be another 100 or more. So finding a new one alone is not surprising. But the discovery of ST7 demonstrates a new paradigm in molecular genetics research now that the first draft sequence of the entire human genome is available. In the past, the discovery of a new tumor suppressor gene would require a major effort involving many scientists, often in several laboratories, working for several years. ST7 was discovered by a single post-doctoral scientist using the new tools provided by the Human Genome Project.

"This finding is an excellent example of how individual researchers, aided by the availability of the near-complete sequence of the human genome, can make major advances in our knowledge of the genetic basis of disease in a matter of a few years or less," says NHGRI Director Francis S. Collins, M.D., Ph.D.

The finding also shows how the information in the human genome sequence enables scientists in different fields to make research contributions far beyond their own specialty, says NHGRI scientific director Jeffrey M. Trent, Ph.D. "Dr. Green's laboratory has been heavily involved in mapping and sequencing human chromosome 7 for the Human Genome Project," he says. "In the last four years, Green's lab directly participated in the identification of genes involved in deafness, vascular disease, and now cancer."

The current research began in 1993 with the doctoral studies of lead author Jean Claude Zenklusen, Ph.D. While working in the lab of co-author Dr. Claudio Conti at the M.D. Anderson Cancer Center's Department of Carcinogenesis, Zenklusen generated a large body of evidence that the long arm of chromosome 7 harbored a tumor suppressor gene. After moving to NHGRI in 1996, Zenklusen began using the genetic maps and DNA sequence of chromosome 7 that were provided by the Human Genome Project. Using a technique called positional cloning, Zenklusen narrowed down his search to a few genes. He then pain-stakingly studied each gene for mutations in cancer cells and found defects in ST7 in several instances. The study included several functional analyses, such as one in which Zenklusen inserted a normal copy of the gene into tumor cells with defective ST7. The genetic treatment eliminated the cancer cells' ability to produce tumors in mice.

The researchers still don't know exactly what the gene does. "ST7 has no relatives or structural similarities to any other known gene," Zenklusen says. But the scientists have shown that the gene has been highly conserved over evolution, since it is widely found in lower organisms. That generally means the gene plays an important function in the body.

Preliminary evidence suggests that ST7 may be involved in regulating the growth of blood vessels into a tumor, a process called angiogenesis. "If ST7 is involved in regulating angiogenesis, it may prove to be a target for developing drugs that would interfere with that process," Zenklusen says. "Without an adequate blood supply, a tumor withers away and dies. So theoretically, if you could prevent angiogenesis, you might be able to come up with a way to kill the tumor without harming the patient."

Zenklusen, Conti and Green, are co-authors of the paper, "Mutational and functional analyses reveal that ST7 is a highly conserved tumor suppressor gene on human chromosome 7q31," which appears in the April issue of the journal Nature Genetics (Vol. 27, No. 4).

NIH/National Human Genome Research Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to