• Press Release

Genetic Material Once Considered Junk Actually Could Hold Key to Cancer Drug Response, Mount Sinai Researchers Find

  • New York, NY
  • (April 03, 2018)

Material left out of common processes for sequencing genetic material in cancer tumors may actually carry important information about why only some people respond to immunotherapy, possibly offering better insight than the type of material that is being sequenced, according to a study by Mount Sinai researchers published on April 3 in Cell Reports.

Sequencing a type of genetic material in cancer tumors called messenger RNA has transformed personalized cancer therapy and revealed biomarkers for early detection. Advances in this field have transformed scientists’ understanding of the differences between healthy tissue and tumors.

To date, gene expression in tumors has been typically profiled by capturing messenger RNAs; however, they represent only a fraction of the molecules detected. A different type of RNA, called non-coding RNA, had long been dismissed as “junk” and left out of sequencing processes. However, recent advances in genetics have shown that many non-coding RNAs can carry critical functions for cell biology, and a class of RNA known as repetitive elements may interact with the immune system in a way that may be important to develop new and personalized cancer immunotherapies.

In their study, the researchers used a process called total RNA sequencing to identify many non-coding RNAs that would normally remain undetected with the more common sequencing method. They showed that several of these RNAs were specifically expressed in tumors that responded to checkpoint blockade immunotherapy in bladder cancer patients, while others were associated with tumors that escaped being sensed by the immune system.

"Our conclusions make the case that non-coding RNA in tumors, particularly repetitive elements, is under-quantified," said the study's senior author, Benjamin Greenbaum, PhD, Assistant Professor of Oncological Sciences, Pathology, and Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. “We feel that critical findings will arise from analysis of the full breadth of a tumor’s non-coding RNA interplay with the immune system."

One specific finding of this study was that one repetitive element in non-coding RNA is a better predictor of immunotherapy response to PDL1 inhibitors, a type of cancer immunotherapy drug, than conventional immune signatures in certain patients. Mount Sinai researchers, in partnership with the Ting Lab at the Massachusetts General Hospital Cancer Center, found that these repeat RNAs appear to alter the immune response in colon and pancreatic cancers. These have implications for future research on how non-coding RNA could be novel targets for cancer therapy and how they influence patients’ response to cancer therapies.

Researchers from Massachusetts General Hospital and Memorial Sloan-Kettering Cancer Center played critical roles in this research.

This research was supported by grants from the Ludwig Center for Cancer Research, the National Institutes of Health(NIH)/National Cancer Institute Cancer Center Support Grant P30 CA008748, Stand Up to Cancer, the Lustgarten Foundation, the National Science Foundation Grant 1545935, NIH grant K12CA087723-11A1, the Burroughs Wellcome Fund, Affymetrix, Inc., NIH grant P01CA087497-1 and the V foundation.

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 48,000 employees working across eight hospitals, more than 400 outpatient practices, more than 600 research and clinical 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 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

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