Bonanza of genomic sequence data gives researchers valuable new insights into a poorly understood cancer

September 12, 2012
Gastric cancer: Tracking a mysterious killer
The human stomach — cancer in this organ has a low profile but a high death rate. Credit: iStockphoto.com/IngramPublishing

Stomach cancer doesn't get the same publicity as lung or breast cancer, but it is a health threat to be taken very seriously. "Gastric cancer is the second leading cause of worldwide cancer mortality, with an annual death rate of over 700,000 individuals," explains Patrick Tan of the A*STAR Genome Institute of Singapore. He notes that this disease is especially prevalent in Asia; gastric cancer is the fifth most common cancer amongst Singaporean men.

Remarkably little is known about the biological triggers of gastric tumor formation. Tan recently led a large international team of researchers that identified for this particular cancer. They performed a massive dragnet screen for mutations, sequencing 18,000 genes in 15 different tumors and comparing them against equivalent sequences from adjacent, noncancerous tissue.

The results proved illuminating. For example, although half of all gastric cancer cases are associated with infection by the , there were no obvious differences in mutational profiles from H. pylori-positive and -negative tumors. However, Tan notes that this may also be a result of limited sample size. In general, the researchers encountered striking diversity across their samples, but also uncovered patterns upon closer examination. "Although most individual genes were only mutated in a small proportion of samples—usually less than 10%—many of the genetic abnormalities represented different components of the same functional pathway," says Tan.

Many mutations observed by the team affect cellular adhesion pathways, which can influence tumor progression and metastasis. One gene in this pathway, FAT4, caught the researchers' attention; laboratory experiments confirmed that disruption of this gene confers tumorigenic properties on cells. Tan and co-workers subsequently identified FAT4 mutations in genomic data from various other cancers as well. They also identified another previously unknown tumor suppressor gene, ARID1A; importantly, this gene acts in a cancer-associated signaling pathway targeted by existing drugs, suggesting that it may provide a clinically useful indicator for planning patient treatment.

In their ongoing analysis of the gastric cancer genomic landscape, Tan and his co-workers will now investigate major structural alterations—including chunks of chromosome that have been duplicated, deleted or flipped around—as well as changes in how chromosomal DNA becomes chemically modified. Collectively, these data may eventually provide a handy atlas for oncologists. "We hope to apply these technologies to patients treated in clinical trials, to identify accurate molecular predictors of disease relapse and treatment response," says Tan.

Explore further: Experts identify critical genes mutated in stomach cancer

More information: Zang, Z. J., Cutcutache, I., Poon, S. L., Zhang, S. L., McPherson, J. R., et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nature Genetics 44, 570–574 (2012). www.nature.com/ng/journal/v44/n5/abs/ng.2246.html

Related Stories

Experts identify critical genes mutated in stomach cancer

April 8, 2012
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 ...

Genetic differences distinguish stomach cancers, treatment response

August 1, 2011
Stomach cancer is actually two distinct disease variations based on its genetic makeup, and each responds differently to chemotherapy, according to an international team of scientists led by researchers at Duke-National University ...

Stomach bacterium damages human DNA

September 6, 2011
The stomach bacterium Helicobacter pylori is one of the biggest risk factors for the development of gastric cancer, the third most common cause of cancer-related deaths in the world. Molecular biologists from the University ...

Recommended for you

An architect gene is involved in the assimilation of breast milk

October 17, 2017
A family of "architect" genes called Hox coordinates the formation of organs and limbs during embryonic life. Geneticists from the University of Geneva (UNIGE) and the Swiss Federal Institute of Technology in Lausanne (EPFL), ...

Study identifies genes responsible for diversity of human skin colors

October 12, 2017
Human populations feature a broad palette of skin tones. But until now, few genes have been shown to contribute to normal variation in skin color, and these had primarily been discovered through studies of European populations.

Genes critical for hearing identified

October 12, 2017
Fifty-two previously unidentified genes that are critical for hearing have been found by testing over 3,000 mouse genes. The newly discovered genes will provide insights into the causes of hearing loss in humans, say scientists ...

Team completes atlas of human DNA differences that influence gene expression

October 11, 2017
Researchers funded by the National Institutes of Health (NIH) have completed a detailed atlas documenting the stretches of human DNA that influence gene expression - a key way in which a person's genome gives rise to an observable ...

Genetic advance for male birth control

October 10, 2017
When it comes to birth control, many males turn to two options: condoms or vasectomies. While the two choices are effective, both methods merely focus on blocking the transportation of sperm.

Researchers uncover new congenital heart disease genes

October 9, 2017
Approximately one in every 100 babies is born with congenital heart disease (CHD), and CHD remains the leading cause of mortality from birth defects. Although advancements in surgery and care have improved rates of survival ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.