Over 600 genes found mutated in stomach cancer

A large-scale genomics study led by researchers from the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore and National Cancer Centre Singapore (NCCS) identified more than 600 mutated genes in stomach cancer. Published in the May issue of Nature Genetics, the study spells hope for improved treatments tailored to the genetic constitution of individual stomach tumours.

Stomach cancer is the second deadliest type of cancer in the world, accounting for more than 700,000 deaths each year. The disease is often hard to treat due to late detection of tumours and a poor understanding of its causes. “Until now, the genetic abnormalities that cause stomach cancers are still largely unknown, which partially explain the overall poor treatment outcome,” said Associate Professor Patrick Tan from Duke-NUS, a senior author of the study.

“Our study is one of the first gastric cancer studies to investigate the vast majority of human genes at the single nucleotide level. We screened 18,000 human genes and identified over 600 genes that were previously unknown to be mutated in stomach cancer,” said Professor Teh Bin Tean, another senior author from Duke-NUS and NCCS. The team discovered the novel gene mutations upon analysing tumour and normal tissue from stomach cancer patients using state-of-the-art DNA sequencing technology.

The team discovered the novel gene mutations upon analysing tumour and normal tissue from stomach cancer patients using state-of-the-art DNA equencing technology.

They found two of the 600 genes, FAT4 and ARID1A, particularly interesting. A further analysis of about 100 stomach tumours found the two genes to be mutated in five per cent and eight per cent of stomach cancers, respectively. In some patients, portions of the chromosome containing the two genes were found to be missing, which is added evidence that genetic defects affecting these genes often exist in stomach cancer.

Lab experiments also showed that manipulation of the FAT4 and ARID1A function altered the growth of stomach cancer cells. Noting that ARID1A and FAT4 are likely involved in many other cancer types as well, the team is actively studying the clinical implications of their findings.

With more than 100,000 new cases of stomach cancer each year likely to be caused by mutations in FAT4 or ARID1A, drugs against these targets may someday lead to more effective treatment of stomach tumours and other cancers.

Besides Duke-NUS and NCCS, the international team of scientists and clinicians also hail from the Cancer Science Institute of Singapore at NUS; Genome Institute of Singapore; NUS Graduate School for Integrative Sciences and Engineering; NUS’ Yong Loo Lin School of Medicine; Singapore General Hospital; Singapore-MIT Alliance for Research and Technology; Van Andel Research Institute and Northwestern University in the US; Yonsei University in South Korea; as well as Queen’s University and the Wellcome Trust Sanger Institute in the UK.

Extracted from NUS' Knowledge Enterprise Online -May/June 2012