GIS analysis technique shows abnormal gene structures in cancer tumours
Singapore—Scientists at A*STAR’s Genome Institute of Singapore (GIS) have developed a technology that shows how genes in healthy stomach cells are altered when they become cancerous. The study was reported in the scientific journal, Nature Communications on 10th July 2014.
According to the World Health Organization, stomach cancer, also known as gastric cancer, is a major cause of cancer death worldwide[1]. In order to find a cure for stomach cancer, it is important to find more efficient ways to study how genes mutate into cancerous cells from healthy stomach cells.
Current methods being conducted to study protein-DNA interactions in cancerous stomach cells require large amounts of DNA. A group of scientists, led by Prof Patrick Tan, Principal Investigator of the Cancer Therapeutics and Stratified Oncology laboratory at GIS, have developed a technique to study the same reactions using far less DNA amounts. This allows them to analyse tissue samples directly from human patients, making their technique more efficient than current methods. The scientists achieved this by successfully applying a technique known as Nano-Chromatin immuneprecipitation sequencing (Nano-ChIPseq) to stomach tumour cells.
When using the Nano-ChIPseq technique, the scientists found that stomach tumours exhibited a strong tendency to carry abnormal modifications in the beginning regions[2], also known as cryptic promoters. Hence, they propose using cryptic promoters as a potential targetfor developing anti-cancer treatments for stomach cancer. The technique developed at GIS can detect stomach cancer cells using smaller amounts of tissue – making it more efficient in testing for stomach cancer. Therefore, the scientists propose the technique to be further developed into a diagnostic tool for stomach cancer.
Prof Tan said, “Our group applies the tools in cancer genomics to analyse stomach cancer. Using the latest DNA sequencing technologies developed in our institute, the tumour cells are comprehensively analysed to identify molecular differences between cancer cells and normal tissues. More importantly, due to quantum leaps in the scale and throughput of DNA and biocomputing technologies, complete human genomes can now be sequenced in only a few days, at a very low cost. Compare this: the original human genome project which was completed in the early 2000s required billions of dollars and hundreds of researchers. Today, thousands of tumours can be sequenced, analysed and shared by relatively small academic laboratories.”
“There are several types of cancer that occur more frequently in Asia than in the West,” said Prof Ng Huck Hui, Executive Director of GIS. “These include stomach and liver cancer. Comparatively little is known about the underlying biology of these Asian cancers. Reflecting the lack of understanding, these cancers typically have very poor prognosis. Hence, there is this urgent need for us to apply the latest scientific techniques to develop better ways to diagnose and treat Asian cancers. What is even more promising about this important work by Prof Tan and his team is that the technology used here can also be broadly applied to other disease domains and pathologic conditions, since epigenomic changes occur in all human diseases. I congratulate Prof Tan and his team for this magnificent work.”
“This study addresses one of today’s most perplexing questions in cancer research – why some cancers have no or a limited number of cancer-causing mutations,” added Prof Toshikazu Ushijima, Chief, Division of Epigenomics, National Cancer Center Research Institute, Japan. “Using a highly-advanced analytical method developed in Singapore, the researchers demonstrated that embryonic genes are regenerated in cancer cells. The phenomenon itself may change the way we analyse cancer cells, and the list of regenerated genes may contain novel therapeutic targets. I am most impressed by the network of world-leading scientists and clinicians in Singapore.”
Other organisations involved in the study include Duke-NUS Graduate Medical School (Singapore), Cancer Science Institute of Singapore, and the Singapore Gastric Cancer Consortium.
Prof Patrick Tan is also the Senior Principal Investigator at the Cancer Science Institute of Singapore, NUS; Professor at the Duke-NUS Graduate Medical School;
and Principal Investigator (Adjunct) at the National Cancer Centre (Singapore).
Notes to Editor:
The research findings described in the media release can be found in the Nature Communications journal, under the title, “Nanoscale Chromatin Profiling of Gastric Adenocarcinoma Reveals Cancer-Associated Cryptic Promoters and Somatically Acquired Regulatory Elements” by Masafumi Muratani1,*, Niantao Deng2,3, Wen Fong Ooi1, Suling Joyce Lin1, Manjie Xing2,3, Chang Xu4, Aditi Qamra1,5, Su Ting Tay2,6, Simeen Malik2, Jeanie Wu6, Ming Hui Lee6, Shenli Zhang2, Luke Lin Chuen Tan2, Huihoon Chua1, Wai Keong Wong7, Hock Soo Ong7, London Lucien Ooi7, Pierce Kah-How Chow7,8,9, Weng Hoong Chan7, Khee Chee Soo8, Liang Kee Goh2, Steve Rozen2, Bin Tean Teh2,4,10, Qiang Yu1, Huck Hui Ng11 & Patrick Tan1,2,4,6
1 Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
2 Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
3 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.
4 Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, #12-01, Singapore 117599, Singapore.
5 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive #04-01, Singapore 117597, Singapore.
6 Cellular and Molecular Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
7 Department of General Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
8 Department of Surgical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
9 Office of Clinical Sciences, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
10 Laboratory of Cancer Epigenome, Department of Medical Sciences, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
11 Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, Singapore 138672, Singapore.
* Present address: Department of Genome Biology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
For media queries and clarifications, please contact:
Ms Winnie Lim
Head
Office of Corporate Communications
Genome Institute of Singapore, A*STAR
Tel: +65 6808 8013
About the Genome Institute of Singapore (GIS)
The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards academic, economic and societal impact.
The key research areas at the GIS include Human Genetics, Infectious Diseases, Cancer Therapeutics and Stratified Oncology, Stem Cell and Developmental Biology, Cancer Stem Cell Biology, Computational and Systems Biology, and Translational Research.
The genomics infrastructure at the GIS is utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.
In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore’s manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.
A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR’s research entities as well as a growing number of corporate laboratories.
[1] Key facts: Cancer Fact Sheet No297, February 2014, World Health Organization
[2] The beginning regions refer to specific parts of genes responsible for maintaining the structural integrity of the genome.
