Gastric cancers show RNA editing dysregulation

Last Updated: 2016-07-26

By David Douglas

NEW YORK (Reuters Health) - Sequence alterations at the RNA but not DNA level, primarily mediated by adenosine deaminase enzymes that act on RNA (ADAR), are apparent in almost all gastric cancer tissues, according to multinational researchers.

As Dr. Leilei Chen told Reuters Health by email, "Identifying molecular aberrations in gastric cancer may improve our understanding of gastric carcinogenesis; identify strategies for subdividing patients into biologically and clinically relevant subgroups and highlight novel RNA-based therapeutic opportunities."

Dr. Chen of the National University of Singapore and colleagues recently reported important roles for ADAR-mediated RNA-editing in liver and esophageal cancers in humans.

To dissect the relationship between RNA editing and gastric cancer prognosis and progression, the team used high-throughput transcriptome sequencing of primary gastric cancers and cell lines.

According to a report June 30 online in Gastroenterology, compared to normal tissue, there was a genomic gain of the ADAR1 and loss of the ADAR2 gene in primary gastric cancers.

In fact, based on gastric cancer microarray examination, compared to patients who had neither or only one such dysregulation, patients with ADAR1 overexpression and ADAR2 downregulation had the shortest overall survival times.

The results were validated in an independent microarray cohort of 432 gastric cancers profiled on a completely separate microarray platform.

These and other findings, say the investigators, indicate that "ADAR1 overexpression concomitant with ADAR2 downregulation is associated with poor prognosis."

Thus, the researchers point out, "by comparing editing levels at different stages of gastric lesions along the normal to cancer continuum, we observed increasing levels of RNA editing dysregulation from normal gastric tissues, to pre-malignant intestinal metaplasia, and finally clinically verified gastric cancer samples."

Most mutational studies have focused at the DNA level, they say, whereas the current study "demonstrates that differentially expressed ADARs in gastric tumors with consequent adenosine-to-inosine RNA editing dysregulation, may serve as a second layer of 'somatic mutations' and a novel contributor to gastric cancer."

SOURCE: http://bit.ly/2ao1Si7

Gastroenterology 2016.