Experts Identify Critical Genes Mutated in Stomach Cancer, Duke-NUS and National Cancer Center Singapore (NCCS) Study

Published: Apr 09, 2012

SINGAPORE, April 8, 2012 – An international team of scientists, led by researchers from Duke-NUS Graduate Medical School (Duke-NUS) in Singapore and the National Cancer Center Singapore (NCCS), has identified hundreds of novel genes that are mutated in stomach cancer, the second-most lethal cancer worldwide.

The study, which appears online on April 8, 2012 in Nature Genetics, paves the way for treatments tailored to the genetic make-up of individual stomach tumors.

Stomach cancer is the second leading cause of cancer death globally with more than 700,000 deaths each year, and is particularly common in East Asia. Treatment of this deadly disease is often difficult and unsuccessful because of late detection of tumors and a poor understanding of the causes of stomach cancer. In the United States, less than quarter of patients survive more than five years after diagnosis, even after treatment.

Using state-of-the-art DNA sequencing technology, the research team analyzed tumor and normal tissue from stomach cancer patients, which led to the discovery of the novel gene mutations.

Two of the 600 stomach cancer-associated genes identified, FAT4 and ARID1A, proved to be particularly interesting. A further analysis of about 100 stomach tumors found these genes to be mutated in 5% and 8% of stomach cancers, respectively. In some patients, portions of the chromosome containing the two genes were found to be missing, further evidence that genetic defects affecting these genes occur frequently in stomach cancer.

Experiments in the lab demonstrated the importance of these two genes in driving stomach cancer, as manipulation of FAT4 and ARID1A function altered the growth of stomach cancer cells.

In addition to Duke-NUS and the National Cancer Center Singapore, the study also involved collaborators from the Cancer Science Institute of Singapore; Genome Institute of Singapore; National University of Singapore; Singapore General Hospital; Van Andel Research Institute, Michigan, USA; Northwestern University, Chicago, USA; Yonsei Cancer Center, Seoul, South Korea; Queen’s University, Belfast, UK; and Welcome Trust Sanger Institute, Hinxton, UK.

Support for this study was provided by the National Medical Research Council, as part of the Singapore Gastric Cancer Consortium. Funding was also received from the Cancer Science Institute of Singapore, Duke-NUS Graduate Medical School, Genome Institute of Singapore (Agency for Science, Technology and Research), and the Lee Foundation.

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