Gene Mutation Found for Aggressive Form of Pancreatic Cancer
Researchers have identified a mutated gene common to adenosquamous carcinoma tumors, the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer. The findings by Liu et al are published in Nature 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. Adenosquamous carcinoma cases are infrequent, but typically have a worse prognosis than more common types of pancreatic cancer.
“There has been little progress in understanding pancreatic [adenosquamous carcinoma] since these aggressive tumors were first described more than a century ago,” said co–senior author Miles F. Wilkinson, PhD, Professor in the Department of Reproductive Medicine at University of California, San Diego, School of Medicine, and a member of the UC San Diego Institute for Genomic Medicine. “One problem has been identifying mutations unique to this class of tumors.”
Study Details
In their paper, Dr. Wilkinson, co–senior author Yanjun Lu, PhD, of Tongji University in China, and colleagues report that adenosquamous carcinoma pancreatic tumors have somatic or nonheritable mutations in the UPF1 gene, which is involved in a highly conserved RNA degradation pathway called nonsense-mediated RNA decay. It is the first known example of genetic alterations in a nonsense-mediated RNA decay gene in human tumors.
Nonsense-mediated RNA decay has two major roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA). Second, it degrades a specific group of normal mRNAs, including those encoding proteins promoting cell growth, cell migration and cell survival. Loss of nonsense-mediated RNA decay in these tumors may “release the brakes on these molecules, and thereby driving tumor growth and spread,” said Dr. Wilkinson.
According to co–first author Rachid Karam, MD, PhD, a postdoctoral fellow in Dr. Wilkinson’s laboratory, 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,” Dr. Karam said.
Drs. Wilkinson and Lu are the corresponding authors for the Nature Medicine article.
Funding for this research came, in part, from The National Key Basic Research Program of China, the National Natural Science Foundation of China and the National Institutes of Health. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
