Scientists Uncover Valuable Gene Activity for Precancerous Cysts, Cancer in Pancreas

A Wilmot Cancer Institute study revealed the actions of a key gene and its surrounding network that causes cysts in the pancreas, as well as how cancer arises from the cysts. The work could someday lead to new treatments based on the molecular information.

Researchers focused on a gene known at Arid1a. The next step is to determine whether a subset of pancreas cancer patients with that gene mutation might benefit from a precision approach to treatment. It’s an important development for a lethal disease that’s often discovered in advanced stages and is usually resistant to chemotherapy, said senior author Aram F. Hezel, M.D., the John and Ethel Heselden Professor and chief of Hematology/Oncology at Wilmot.

“Studies show that mutations in Arid1a are also implicated in other GI cancers with a poorer prognosis,” Hezel said. “We attempted to understand how that gene network impacts cancer’s behavior, and to explore how cancer drugs such as imatinib (Gleevec), among other agents, might be helpful for patients with these types of mutations.”

The team uncovered the importance of Arid1a in normal pancreatic function, and then investigated what happened when gene expression was lost and other known cancer genes were present to fuel the disease. In mouse models of pancreatic cancer, for example, loss of Arid1a led to the common cystic condition, known as IPMN or intraductal papillary mucinous neoplasm. Some IPMN are benign but others should be removed because of the risk of becoming cancerous; the role of Arid1a in establishing IPMN was significant.

The study is published in Gut, a British Medical Journal. Wenjia Wang, M.D., Ph.D., senior instructor in Oncology and Hematology at Wilmot, led the research with Scott Friedland, an M.D./Ph.D. student. Read the full scientific study.

Funding was provided by the Pancreatic Cancer Association of Western New York, which has its annual fundraising 5K in November; the National Cancer Institute; the local Michael Contestable Golf Tournament; and the Wilmot Cancer Research Fellowship Program. Other collaborators from the University of Rochester Medical Center included Laurie Steiner M.D., associate professor of Pediatrics; Christa Whitney-Miller, M.D., associate director of Surgical Pathology and an associate professor of Pathology; Diana Agostini-Vulaj, D.O., assistant professor of Pathology; and Aaron Huber, D.O., assistant professor of Pathology.

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