Discovering a Major Factor Causing Aggressive Cancer

Researchers from the University of Otago have identified a crucial factor that contributes to the aggressive spread of colon cancer, marking a significant advancement in the fight against fatal tumors.

Researchers, led by Associate Professor Aniruddha Chatterjee and Doctors Euan Rodger and Rachel Purcell, found anomalies in the DNA instruction code that cause colorectal (bowel) cancer, the second-leading cause of cancer-related death in Aotearoa, to develop aggressively.

The discovery, which was reported in the Cell Press journal iScience, is a critical step toward the identification and prevention of tumors that spread or advance rapidly, according to Dr Rodger.

The spread of tumors to distant organs, known as metastasis, is the leading 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 Euan Rodger, Senior Research Fellow, Department of Pathology, University of Otago

Methylation, a chemical change of DNA, has the ability to control how the DNA code behaves in a cell. Thus, investigating DNA methylation levels (also known as the epigenetic code) in the lab and patient tumor samples has the potential to better understand metastasis and use the knowledge to assist patients.

The study looked at the DNA methylation map as well as how DNA behaves in bowel cancer patients. They next examined clinical samples from primary colon tumors and tumors that had migrated to the liver in each of the 20 patients.

Dr Rodger added, “We have discovered almost 300 gene regions that show distinct DNA methylation levels in liver metastasis. 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 discovery is especially noteworthy for Aotearoa, where 1,200 people die from colon cancer each year.

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.”

Aniruddha Chatterjee, Associate Professor, University of Otago

“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,” Chatterjee added.