“Cryptic Promoters” Drive Stomach Cancer

Using a new technique called Nano-ChIPseq, scientists have found that stomach cancer is driven by mutations in regions of the genome known as cryptic promoters.

AsianScientist (Jul 11, 2014) – Scientists at A*STAR’s Genome Institute of Singapore (GIS) have developed a technology that shows how genes in healthy stomach cells are altered when they become cancerous. The study has been published in the journal Nature Communications.

Stomach cancer, also known as gastric cancer, is a major cause of cancer death worldwide. Scientists have sought more efficient ways to study how genes mutate into cancerous cells from healthy stomach cells. However, current methods used to study protein-DNA interactions in cancerous stomach cells require large amounts of DNA.

A research group, led by Professor Patrick Tan, Principal Investigator of the Cancer Therapeutics and Stratified Oncology laboratory at GIS, have developed a technique to study the same reactions using far less DNA. This allowed them to analyse tissue samples directly from human patients, making their technique more efficient than current methods. The scientists achieved this by successfully applying a technique known as Nano-Chromatin immuneprecipitation sequencing (Nano-ChIPseq) to stomach tumour cells.

“Using the latest DNA sequencing technologies developed in our institute, the tumour cells are comprehensively analysed to identify molecular differences between cancer cells and normal tissues. More importantly, 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,” Prof Tan said.

“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.”

Using the Nano-ChIPseq technique, the research team found that stomach tumours exhibited a strong tendency to carry abnormal modifications in genetic regions known as cryptic promoters. These cryptic promoters drive the expression of gastric cancer-related genes, but also those involved in embryonic development and tissue specification. Based on their findings, the group proposes using cryptic promoters as a potential target for developing anti-cancer treatments for stomach cancer.

“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,” added Prof Toshikazu Ushijima, Chief, Division of Epigenomics, National Cancer Center Research Institute, Japan.

“Using a highly-advanced analytical method developed in Singapore, the researchers demonstrated that embryonic genes are regenerated in cancer cells. The phenomenon itself may change the way we analyse cancer cells, and the list of regenerated genes may contain novel therapeutic targets.”

The article can be found at: Muratani et al. (2014) Nanoscale Chromatin Profiling of Gastric Adenocarcinoma Reveals Cancer-associated Cryptic Promoters and Somatically Acquired Regulatory Elements.


Source: A*STAR; Photo: Ed Uthman/Flickr/CC.
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