Asian Scientist (Nov. 14, 2013) – A team of scientists from Singapore, Thailand, and Romania have achieved a breakthrough in understanding the molecular basis of bile duct cancer or cholangiocarcinoma (CCA), a rare but highly lethal form of liver cancer. They did this by using advanced DNA sequencing technologies to map the complete repertoire of human genes disrupted in cholangiocarcinoma.
The team’s findings, published in Nature Genetics, may lead to more effective cholangiocarcinoma treatments, and have shed light on some of the oldest questions in cancer research.
CCA is a cancer involving uncontrolled growth of the bile ducts, the part of the liver that drains bile into the intestine. It is considered a rare cancer in most countries, but its incidence has been rising worldwide and CCA is widespread in certain countries such as the North East of Thailand and neighboring Laos because of exposure to liver flukes. Some of the potential causes of CCA include bile duct inflammation, congenital cysts, hepatitis, and the presence of liver stones.
By studying CCA cases from Singapore, Thailand and Romania, the team identified several genes that were repeatedly disrupted in order for CCA to develop. Importantly, the cellular pathways controlled by these genes have suggested new potential avenues to treat CCA.
One of the genes identified, BAP1, participates in the unpacking of DNA, and drugs targeting this process (called “chromatin modifier drugs”) are being developed.
“While further research needs to be done, this may pave the way for identifying which bile-duct cancer patients may benefit from chromatin-modifier drugs,” said Professor Teh Bin Tean, a co-senior author of the study.
Findings from the study have also deepened our basic understanding of how cancer develops.
“A poorly-understood question in cancer research is whether different carcinogens, applied to the same cancer type, will cause disruptions in the same sets of genes, or if different carcinogens will cause different type of genes to be disrupted,” said co-senior author Professor Steve Rozen.
According to the researchers, their study of CCA can be used to answer these questions, as CCAs are caused by different carcinogenic exposure in different parts of the world.
The team found that while CCAs from Thailand, Singapore and Romania appeared to be very similar when observed under the microscope, they were in fact very different when analyzed at the molecular level. This finding provides one of the first key pieces of evidence that different types of carcinogen exposures, although acting on the same type of tissue, are associated with disruptions in different sets of genes.
According to co-senior author Professor Patrick Tan, these findings have practical applications as well. “Based on these results, it may be possible to investigate a patient’s cancer and by looking at the types of disrupted genes, infer what caused the cancer.”
Such information would have major implications for cancer prevention efforts.
Source: National Cancer Centre Singapore; Photo: MonsieurLui/Flickr/CC.
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