Gene Mutation Found for Aggressive Form of Pancreatic Cancer

A mutated gene common to adenosquamous carcinoma tumors has been discovered and is the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer.

Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. There has been little progress in understanding pancreatic ASC, as no mutations unique to this class of pancreatic tumors have been identified.


Scientists at the University of California, San Diego School of Medicine (La Jolla, CA, USA) and an international team evaluated a set of tumors and corresponding normal tissues from 23 patients with ASC of the pancreas, as well as tumors from 24 patients with ductal adenocarcinoma, three patients with solid pseudopapillary neoplasm, two patients with neuroendocrine carcinoma and 21 patients with lung squamous cell carcinoma. Of the 23 ASC patient specimens, there were 19 formalin-fixed, paraffin-embedded (FFPE) tissue sections available. The other four ASC patient specimens were frozen immediately after collection.

Genomic DNA from the frozen samples was extracted using the DNeasy Blood & Tissue Kit (Qiagen; Valencia, CA, USA) and genomic DNA from the FFPE samples was extracted using Qiagen’s QIAamp DNA FFPE Tissue Kit. Quantitative real-time reverse-transcription PCR (RT-qPCR) analysis was performed using the relative quantification method in a RotorGene RG-3000 thermal cycler system (Corbett Research; Mortlake, NSW, Australia).

The investigators found that that ASC pancreatic tumors have somatic or non-heritable mutations in the Up-frameshift 1 (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). Second, it degrades a specific group of normal mRNAs, including those encoding proteins promoting cell growth, cell migration and cell survival.

Miles F. Wilkinson, PhD, co-senior author, said, “There has been little progress in understanding pancreatic ASC since these aggressive tumors were first described more than a century ago. One problem has been identifying mutations unique to this class of tumors.” The study was published on May 25, 2014, in the journal Nature Medicine.

Related Links:
University of California, San Diego School of Medicine
Qiagen
Corbett Research