28th May 2014 Gene mutation found for aggressive form of Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma (ASC) tumours – the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer.
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with more than 45,000 new cases diagnosed and 38,000 deaths annually. It has the lowest survival rate of any cancer, with just 6% of patients living beyond five years. ASC cases are infrequent, but typically have an even worse prognosis than more common types of pancreatic cancer. “There has been little progress in understanding pancreatic ASC since these aggressive tumours were first described more than a century ago,” said co-senior author Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine. “One problem has been identifying mutations unique to this class of tumours.” In their paper, Wilkinson and colleagues report that ASC pancreatic tumours 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 tumours. 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 tumours may “release the brakes on these molecules, and thereby driving tumour growth and spread,” says Wilkinson. Co-first author Rachid Karam, PhD, a postdoctoral fellow in Wilkinson’s laboratory, said the findings will create new opportunities for the development of novel diagnostic approaches and therapeutic strategies for pancreatic cancer. “Currently, pancreatic cancer is detected far too late in most cases for effective treatment, and therapeutic options are limited,” Karam said. The findings are published this week in Nature Medicine.
Comments »
|
