Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma (ASC) tumors—the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer. The findings, published in Nature Medicine, report that ASC pancreatic tumors have somatic or non-heritable mutations in the UPF1 gene, which is involved in a highly conserved RNA degradation pathway called nonsense-mediated RNA decay or NMD. It is the first known example of genetic alterations in an NMD gene in human tumors.
NMD has two major roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA), molecules that help transcribe genetic information into the construction of proteins essential to life. Second, it degrades a specific group of normal mRNAs, including those encoding proteins promoting cell growth, cell migration, and cell survival. Loss of NMD in these tumors may “release the brakes on these molecules, thereby driving tumor growth and spread,” says Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine.
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with roughly 45,220 new cases diagnosed and more than 38,400 deaths annually. Both numbers are rising. ASC cases are infrequent, but typically have a worse prognosis than more common types of pancreatic cancer.
Study coauthor Rachid Karam, MD, PhD, says the findings will create new opportunities for the development of novel diagnostic approaches and therapeutic strategies for targeting pancreatic cancer. “Currently, pancreatic cancer is detected far too late in most cases for effective treatment, and therapeutic options are limited,” says Karam. Read the study abstract.
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