Study of DNA Might Help the Fight Against Aggressive Cancer

Researchers from the University of Otago have identified a key factor that contributes to the rapid spread of colon cancer, which represents a significant advancement in the fight against fatal cancers.

Researchers led by Associate Professor Aniruddha Chatterjee and Drs. Euan Rodger and Rachel Purcell discovered defects in the DNA instruction code that are responsible for the aggressive spread of colorectal (bowel) cancer, which is the second highest cause of cancer-related death in Aotearoa.

According to Dr. Rodger, the discovery, which was recently published in the journal iScience, is a significant step toward the detection and prevention of tumors that grow or spread quickly.

The spread of cancer to distant organs, or metastasis, is the primary cause of cancer-related death.

“Despite this profound impact, how tumors become metastatic and so deadly, and what is different about these tumor cells remains largely unknown. The DNA instructions—the blueprint of a cell—and how and where these instructions go wrong in cancer cells provide important clues in understanding why this happens,” Dr. Rodger says.

Methylation — a chemical modification of DNA — have some control over how the DNA code will act in a cell. As a result, understanding metastasis and applying the knowledge to the benefit of patients can be achieved through laboratory and patient tumor sample studies of DNA methylation levels, which are also referred to as the epigenetic code.

The DNA methylation map and the DNA’s behavior in bowel cancer patients were examined by the research team. In every one of 20 patients, they then broke down clinical samples from the primary colon tumor and the tumors that had spread to the liver.

“We have discovered almost 300 gene regions that show distinct DNA methylation levels in liver metastasis,” he says.

“These changes are unique to aggressive liver metastasis and are not present in primary tumors or in normal colon. The genes that have the unique methylation signature have important functions in cells.

“This work shows that cancer cells could use unique methylation patterns to become aggressive.”

According to Associate Professor Chatterjee, the finding is especially significant for Aotearoa, where bowel cancer causes 1,200 deaths annually.

“Patients with distant metastases, such as liver metastasis as we have studied in this work, unfortunately have very low five-year survival rates.

“Alarmingly, the incidence of colorectal cancer is increasing in people under 50 years old and in Māori and Pasifika populations at a faster rate. Māori and Pasifika are also more likely to present directly to emergency departments with advanced colorectal tumors,” he says.

“Our work will open new avenues for understanding why cancer cells become so aggressive and will lead to better outcome prediction and new targets to treat these tumors in the future.” Associate Professor Chatterjee and Dr. Rodger will undertake more research on metastatic cancers.