Blame your genes for aggressive form of pancreatic cancer

Researchers 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.

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, said there has been little progress in understanding pancreatic ASC since these aggressive tumors were first described more than a century ago, asserting one problem has been identifying mutations unique to this class of tumors.

In their paper, Wilkinson, co-senior author Yanjun Lu, PhD, of Tongji University in China, and colleagues 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.

The findings have been published online in the journal Nature Medicine.