Genomic approach isolated novel new fusion gene, which plays a role in some stomach cancer

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A newly discovered hybrid-gen seems a direct role in some stomach cancer, according to an international team of scientists led by researchers at the Duke-NUS graduate medical school Singapore.

The hybrid gene is a fusion of two separate genes, and is one of the first in gastric cancer, the most deadly malignancy is worldwide after lung cancer. The disease kills an estimated 740,000 people per year, including almost 11,000 annually in the United States.

The discovery of the gene may one day enter doctors use current therapies, plus, more effective way to help development of new drugs and diagnostic tools for stomach cancer.

"This is an extremely exciting area, as it opens a potential role for fusion genes in solid cancer diagnosis active and treatment, similar to the fundamental role played by it in the blood cancers,", said Dr. Patrick Tan, an associate professor in cancer and stem cell biology program at the Duke-NUS graduate medical school Singapore. Tan was principal investigator of the study in the April 6, 2011 published issue of the journal Science translational medicine.

Tan said the research team - which included scientists from the National University of Singapore, National Cancer Centre of Singapore, the genome of Singapore, an Institute Yonsei University College of medicine in Seoul, South Korea, and the Howard University - new genomic approach, used to isolate the gene fusion.

The technology is also a stop for genomic analysis (GBA), referred to was used to identify fusion genes in leukemia, but has had less success in she finds in complex solid tumors.

With the technology to home in on abnormal genes in 133 gastric cancer tumors and cell lines, the Singapore-based research group found evidence for a single genetic errors, which was common to four of the cancer samples.

Search for the error led scientists to the CD44 SLC1A2 fusion genes that caused when two close nearby genes to a mixed. The SLC1A2 gene is associated with the metabolism of the amino acid glutamate, which promotion can work its growth and survival as a fertilizer, while the CD44 gene as a kind of "is on" switch.

Fused into one, seems the CD44 SLC1A2 hybrid fuel stomach tumors. Tan's team estimated that the merger-gen at work in up to 2 percent of the cancers of the stomach can be.

"High-throughput genomic technologies such as sequencing and GBA, we now will find that many fusion cancer gene to express," said Tan. "The current feeling is that while most of you are harmless and" genomic instability noises, cases, such as CD44-SLC1A2, where the fusion genes actively contributes to cancer it can. "

The stomach cancer finding could lead to improved therapies for this subset. As part of the study, the researchers used a gene silencing approach to reduce the CD44-SLC1A2 in be. They found that this caused a reduction in the glutamate levels of cancer cells, and the cells more vulnerable to the effects of cisplatin, a common chemotherapy.

"It suggest that drugs, the SLC1A2 inhibit function to sensitize tumors to chemotherapy," said Tan. "Such glutamate uptake inhibitors are, and we work very hard to test this possibility."

Notes:

In addition to Tan also authors study:

Jiong Tao, Baohua, Huang and Heavenly Yap of the National University of Singapore; Nian Tao Deng, Chia Huey Ooi, Iain Beehuat Tan and Shenli Zhang of the Duke NUS graduate medical school; Kalpana Ramnarayanan, hue Kian Center Oh, Jeanie Wu, Minghui Lee, Siew Hong Leong and Kon Oi Lian of the national cancer of Singapore.

Seong soo Lim, Valère Cacheux and Nallasivam Palanisamy of the Genome Institute of Singapore. Sun young RHA and Hyun cheol Chung of the Yonsei University College of medicine; Duane t. Smoot and Hassan Ashktorab of the Howard University College of medicine.

The study was by the bio-medical research Council and national medical research Council of Singapore, Duke-NUS graduate medical school Singapore and the cancer of Sciences Institute of Singapore finance.

Source:
Sarah Avery
Duke University Medical Center