Singapore Scientists Led By A*STAR’s Genome Institute Of Singapore Identify Four Distinct Mechanisms That Contribute To Gastric Cancers
Scientists at the Genome Institute of Singapore (GIS) headed a study which culminated in the discovery of four processes by which gastric cancer is formed. With gastric cancer being the second most common cause of cancer deaths worldwide (almost 750,000 deaths annually) and also an Asian disease, this poses as an extremely important find.
Using what is known as next-generation sequencing technologies, GIS scientists were able to provide a comprehensive view of the gastric cancer genome, characterizing micro- and macro-scale mutations. This led to the identification of four distinct processes that cause mutations in gastric cancer. One of these was found to have a targeted impact on genes and is potentially triggered by bacterial infection. The other processes were found to have impact throughout the genome, and included oxidative damage processes and the failure of DNA proof-reading mechanisms.
The discovery of the mutative actions of these processes provides essential clues to the formation of gastric cancers, paving the way for diagnostics and targeted therapy.
The findings were published online in the December 2012 issue of Genome Biology. The GIS is a research institute under the umbrella of the Agency for Science, Technology and Research (A*STAR).
First author and GIS Principal Investigator Dr Niranjan Nagarajan said, “Cancers are constantly evolving, and therefore understanding how they do so is important for finding new treatments. Mutational processes in cancer had not previously been shown to have a targeted impact on the genome and on genes. With this study, we show evidence of this for the very first time. This is truly exciting since it moves us a critical step towards understanding and finding a cure for gastric cancer.”
Co-author and GIS Principal Investigator Dr Patrick Tan said, “This is the first time gastric cancers have been analyzed at the whole genome level. This work further showcases the reputation of Singapore as a world-leader in gastric cancer research.” “Our study demonstrates that sequencing gastric tumours not only allows the identification of mutations in the human genome but also reveals microorganisms and their pathogenic gene content,” added Dr Axel Hillmer, GIS Principal Investigator.
GIS Executive Director, Prof Ng Huck Hui said, “”This is a very exciting study that probed into the genomic signature of gastric cancers. Through the analysis of somatic mutations occuring in gastric cancers, this team has identified several interesting genes which have profound implications in cancers.”
The study is a project under the Singapore Gastric Cancer Consortium (SGCC), which comprises:
(a) local collaborators – Genome Institute of Singapore, Cancer Science Institute of Singapore, National Cancer Centre Singapore, National University Cancer Institute, National University Health System, Duke-NUS Graduate Medical School Singapore, Nanyang Technological University, National University of Singapore, Changi General Hospital, National University Hospital, Singapore General Hospital, Tan Tock Seng Hospital; and
(b) international collaborators – Asia-Pacific Group on Gastric Cancer, Clinical Therapeutics Research Group, Gastrome Project, International Cancer Biomarker Consortium.
“Whole-genome reconstruction and mutational signatures in gastric cancer”, Niranjan Nagarajan et al.