Study identifies new gene that drives colon cancer – EurekAlert

New York, NY (October 17, 2022) Researchers at Mount Sinais Tisch Cancer Institute have identified a new gene that is essential to colon cancer growth and found that inflammation in the external environment around the tumor can contribute to the growth of tumor cells. The scientists reported these findings in Nature Communications in October.

This is the first time that scientists have discovered that the environment around a colon cancer tumor can program what is known as a super enhancer, a complex area of DNA with a high concentration of transcriptional machinery that controls whether a cell is malignant.

This super enhancer --the largest 1-2% of all enhancers in the cell -- regulates the gene PDZK1IP1, which was previously not identified as a cancer gene. Once researchers deleted PDZK1IP1, colon cancer growth slowed down, suggesting that PDZK1IP1 and its super enhancer could be targets for anti-cancer therapies.

In the United States, colon cancer is the third most prevalent and second most deadly cancer, said the studys first author Royce Zhou, an MD/PhD student at the Icahn School of Medicine at Mount Sinai. This cancer is reliant on surgery for treatment, and immunotherapies that have revolutionized the treatment of advanced cancer have only worked for a small subset of colon cancer patients. Thats why theres a great need for novel target identification.

This study found that the super enhancer is activated by surrounding inflammation in the tumor microenvironment. The inflammation allows the cancer cells to survive in an environment they otherwise would not. Inflammatory bowel disease is a known risk for colon cancer; this finding could add to the understanding of the mechanism involved.

What this means for most patients with colon cancer is that inflammation thats occurring in the tumor is contributing to the tumors growth. This stresses the importance of understanding what we can do to curb the inflammatory effects in the colon through prevention or understanding what dietary effects might have on the microenvironment in the colon, said senior author Ramon Parsons, MD, PhD, Director of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. In terms of treatment, we have genetic evidence that targeting this gene actually inhibits tumors. By understanding all these different components, we will have better tools to try to prevent the disease.

This discovery was made possible by studying live tumor tissue and surrounding healthy tissue immediately after the surgeries of 15 colon cancer patients. Being able to prepare and analyze live cells allowed researchers to see the tumor microenvironment and the genetic and biologic drivers of colon cancer, Mr. Zhou said.

We had live specimen live cells straight from the operating room that allowed us to immediately measure the epigenetic state of that tumor, Dr. Parsons added. Without that infrastructure here at Mount Sinai, we couldnt have made this discovery.

About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked byU.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology.U.S. News & World ReportsBest Childrens Hospitals ranks Mount Sinai Kravis Children's Hospital among the countrys best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 byU.S. News & World Report's"Best Medical Schools," aligned with aU.S. News & World Report"Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas.NewsweeksThe Worlds Best Smart Hospitals ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

For more information, visithttps://www.mountsinai.orgor find Mount Sinai onFacebook,TwitterandYouTube.

Nature Communications

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Study identifies new gene that drives colon cancer - EurekAlert