Experts identify critical genes mutated in stomach cancer

An international team of scientists, led by researchers from the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore and National Cancer Centre of Singapore, 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. In the United States, less than a quarter of patients survive more than five years after diagnosis, even after treatment.

"Until now, the genetic abnormalities that cause stomach cancers are still largely unknown, which partially explain the overall poor treatment outcome," said Patrick Tan, M.D., Ph.D., senior author of the study and associate professor in the Cancer and Stem Cell Biology Program at Duke-NUS. Tan also leads the Genomic Oncology Program at the Cancer Sciences Institute of Singapore and is a group leader at the Genome Institute of Singapore.

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.

"This technology allows us to read the DNA sequence of the genes in each cancer genome," said co-senior author Steven G. Rozen, Ph.D., who heads the Computational Systems Biology and Human Genetics Laboratory in Duke-NUS. "This is also a major team effort involving both basic scientists and clinicians."

The team included scientists and clinicians from three research groups affiliated with Duke-NUS, including one headed by co-senior author Teh Bin Tean, M.D., Ph.D., director of the NCCS-VARI Translational Research Laboratory at the National Cancer Center Singapore.

HEREDITARY DIFFUSE GASTRIC CANCER (HDGC) Stomach (gastric) cancer is the fourth most common cause of cancer worldwide, and the second leading cause of cancer deaths worldwide. The American Cancer Society has estimated that 21,000 new cases of gastric cancer will be diagnosed in the United States in 2010, and that more than 10,000 Americans would die of gastric cancer during the year. Because gastric cancer is difficult to diagnose, it is often diagnosed at a late stage with a poor prognosis. The treatment for gastric cancer is surgery and chemotherapy. The overall 5-year survival rate is 24.3%.

An estimated 1-3% of cases of gastric cancer are caused by Hereditary Diffuse Gastric Cancer. Hereditary diffuse gastric cancer (HDGC) is an inherited cancer syndrome that leads to an increased risk for both diffuse gastric cancer and lobular breast cancer. Patients who inherit the genetic mutation for HDGC are at high risk for developing gastric cancer at a young age.