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Singapore-led team identifies critical stomach cancer genes

11 April 2012

Singapore researchers who are part of the team making the discovery: (from left) Assoc Prof Steven Rozen and Assoc Prof Tan from Duke-NUS Graduate Medical School, together with Dr Zang Zhi Jiang from NCSS

Photo: Duke-NUS

An international team, led by Singapore scientists at Duke-NUS Graduate Medical School (Duke-NUS) and the National Cancer Centre Singapore (NCCS), has identified hundreds of mutant genes in stomach cancer.

The findings published online in Nature Genetics on April 8 offer hope of customised treatments according to the genetic composition of a patient's gastric tumour.

Stomach cancer is the second deadliest cancer globally, causing more than 700,000 deaths each year. The disease is especially prevalent in East Asia. Due to late detection and a poor understanding of the causes, the survival rate of stomach cancer is poor. For instance in the United States, less than a quarter of patients survive more than five years after diagnosis even after treatment.

The investigators included scientists and clinicians from three research groups affiliated with Duke-NUS and NCCS. The team discovered the gene mutations by analysing tumour and normal tissues from stomach cancer patients using state-of-the-art DNA sequencing technology. They screened 18,000 human genes and pinpointed more than 600 genes that were previously unknown to be mutated in stomach cancer.

Of special interest were the genes FAT4 and ARID1A found to be mutated in 5 and 8 per cent of stomach cancers, respectively. Parts of the chromosome housing the two genes were found to be missing in certain patients, showing that defects in these genes were frequent and play a significant role in stomach cancer.

Assoc Prof Patrick Tan, the senior author of the study from the Cancer and Stem Cell Biology Program at Duke-NUS and the Cancer Science Institute of Singapore, said that ARID1A and FAT4 are likely to be involved in many other cancer types. Drugs against these targets may lead to more effective treatment of stomach tumours and other cancers, but he cautioned that more work will be required to translate the findings to clinical applications.

The multinational study included collaborators from NUS; Cancer Science Institute of Singapore; Genome Institute of Singapore; Singapore General Hospital; Van Andel Research Institute in the US; Northwestern University in Chicago; Yonsei Cancer Center in Seoul; Queen's University in Ireland; and Welcome Trust Sanger Institute in the UK.

Support for this study was provided by the National Medical Research Council, the Cancer Science Institute of Singapore, Duke-NUS Graduate Medical School, Genome Institute of Singapore and the Lee Foundation.