Scientists at A*STAR’s Genome Institute of Singapore (GIS) headed a study that discovered four processes by which gastric cancer is formed. This is extremely important since gastric cancer is the second most common cause of cancer deaths worldwide, claiming almost 750,000 lives annually, 60% of which are Asians.
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. 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 micro-organisms 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 occurring 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 Research Group for Gastric Cancer, Cancer Therapeutics Research Group, Gastrome Project, International Cancer Biomarker Consortium.
The research findings described in the press release can be found in the 13 December 2012 advance online issue of Genome Biology under the title “Whole-genome reconstruction and mutational signatures in gastric cancer”.
Authors: Niranjan Nagarajan1*#, Denis Bertrand1*, Axel M Hillmer2*, Zhi Jiang Zang3,4*, Fei Yao2,5, Pierre-Étienne Jacques1, Audrey SM Teo2, Ioana Cutcutache6, Zhenshui Zhang2, Wah Heng Lee1, Yee Yen Sia2, Song Gao7, Pramila N Ariyaratne1, Andrea Ho2, Xing Yi Woo1, Lavanya Veeravali8, Choon Kiat Ong9, Niantao Deng10, Kartiki V Desai11, Chiea Chuen Khor12,4, Martin L Hibberd12,4, Atif Shahab8, Jaideepraj Rao13, Mengchu Wu14, Ming Teh15, Feng Zhu19, Sze Yung Chin15, Brendan Pang14,15, Jimmy BY So16, Guillaume Bourque17,18, Richie Soong14,15, Wing-Kin Sung1, Bin Tean Teh9, Steven Rozen6,Xiaoan Ruan2, Khay Guan Yeoh19, Patrick BO Tan10,12,14#, Yijun Ruan2,20
1. Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
2. Genome Technology and Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
3. Cellular and Molecular Research, National Cancer Centre, Singapore 169610, Singapore.
4. Cancer and Stem Cell Biology Program, Duke–National University of Singapore (NUS) Graduate Medical School, Singapore 169857, Singapore.
5. Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore.
6. Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
7. NUS Graduate School of Integrative Sciences and Engineering, Centre for Life Sciences, Singapore 117456, Singapore
8. Research Computing, Genome Institute of Singapore, Singapore 138672, Singapore
9. NCCS-VARI Translational Research Laboratory, National Cancer Centre, Singapore 169610, Singapore.
10.Genomic Oncology, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
11.National Institute of Biomedical Genomics, 2nd Floor Netaji Subash Sanatorium, Kalyani 741251 West Bengal, India.
12.Infectious Diseases, Genome Institute of Singapore, Singapore 138672, Singapore.
13.Department of Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore.
14.Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore.
15.Department of Pathology, National University Health System, National University of Singapore, Singapore 119074, Singapore.
16.Department of Surgery, National University Health System, National University of Singapore, Singapore 119074, Singapore.
17.Department of Human Genetics, McGill University, Montréal H3A 1B, Canada.
18.McGill University and Genome Quebec Innovation Center, Montréal H3A 1A4, Canada.
19.Department of Medicine, National University Health System, National University of Singapore, Singapore 119074, Singapore.
20.Department of Biochemistry, National University of Singapore, Singapore 119074, Singapore.
* These authors contributed equally to this work.