Local scientists find out what turns stomach cells cancerous

SINGAPORE — Using a newly developed technique, local researchers have made a breakthrough in stomach cancer research by discovering what turns healthy stomach cells cancerous.

Instead of carrying cancer-causing mutations in genes, the researchers found that stomach cancer cells have normal genes that are being abnormally activated, which causes the cells to turn cancerous.

This was discovered by taking tissue samples from stomach tumours from human patients and analysing their DNA using a new technique developed in Singapore.

“Our group applies the tools in cancer genomics to analyse stomach cancer,” said Professor Patrick Tan of the Cancer Therapeutics and Stratified Oncology laboratory at the Genome Institute of Singapore (GIS), who led the group of local scientists and clinicians that did the research.

“Using the latest DNA sequencing technologies developed at our institute, the tumour cells are comprehensively analysed to identify molecular differences between cancer cells and normal tissue.”

Data from the World Health Organization showed stomach cancer is a major cause of cancer death worldwide. “There are several types of cancer that occur more frequently in Asia than in the West,” said Professor Ng Huck Hui, executive director of GIS. These so-called Asian cancers include stomach and liver cancer, he said.

However, scientists do not understand as much about how these cancers come about and how to treat them, leading them to have poorer prognoses than other cancers. “Hence, there is this urgent need for us to apply the latest scientific techniques to develop better ways to diagnose and treat Asian cancers,” said Prof Ng.

The research, published in the journal Nature Communications this week, found that hundred of genes in stomach tumours were turned on by abnormal modifications to the DNA called cryptic promoters.

Because of these cryptic promoters, the genes are expressed in a way that is similar to how they are expressed in embryonic cells.

“These genes do not carry mutations themselves, but because of their activation via the cryptic promoters, they are likely to contribute to cancer cells displaying many of the embryonic-type properties commonly observed in tumours, including stomach cancer,” said Prof Tan.

These identified cryptic promoters are thus a promising target for developing treatments against stomach cancer, the researchers said.

“This study addresses one of today’s most perplexing questions in cancer research — why some cancers have no or a limited number of cancer-causing mutations,” said Professor Toshikazu Ushijima, the chief of the epigenomics division of the National Cancer Center Research Institute in Japan, who was not involved in the research.

He added that the discovery that embryonic genes are being regenerated in cancer cells may change the way we analyse cancer cells in the future.

A WIDER APPLICATION FOR DISEASE RESEARCH

The ramifications of the group’s research extend to beyond cancer, as the techniques developed could help scientists studying other diseases.

Prof Ng said: “What is even more promising about this important work by Prof Tan and his team is that the technology used here can also be broadly applied to other disease domains and pathologic conditions, since epigenomic changes occur in all human diseases.”

Current methods for studying protein-DNA interactions in cancerous stomach cells require large amounts of DNA. For their study, the scientists developed an advanced technique called nano-chromatin Immunoprecipitation sequencing (Nano-ChIPseq), which requires far less DNA to work.

This allowed them to take small tissue samples of tumours directly from human patients and analyse them, making their technique more efficient and direct.

The success of their technique bodes well for the future of cancer — and genomic — research, the scientists said.

“Due to quantum leaps in the scale and throughput of DNA and biocomputing technologies, complete human genomes can now be sequenced in only a few days, at a very low cost,” said Prof Tan.

“Compare this: The original Human Genome Project, which was completed in the early 2000s, required billions of dollars and hundreds of researchers. Today, thousands of tumours can be sequenced, analysed and shared by relatively small academic laboratories.”