‘Revolutionary’ study reveals new cause

Australian cancer researchers have identified an important new link between a person’s cancer risk and the function of circular RNAs, a recently discovered family of gene segments found in cells.

New research led by Flinders University was announced in cancer cell, The paper, in one of the world’s top cancer journals, found that a specific circular RNA found in many of us can attach to the DNA in our cells and cause DNA mutations that can lead to cancer. I discovered that

“Environmental and genetic factors have long been thought to be the main causes of cancer, but this revolutionary discovery is the discovery that we are using ER3D (from ‘endogenous RNA-induced DNA damage’) It ushers in an entirely new field of medical and molecular biology research. says Flinders University Professor Simon KongHe leads circular RNA in the cancer lab at the Flinders Institute of Health and Medicine.

“This is the first example that a genetic molecule present in many of us has the ability to mutate our own DNA and cause cancer from within.

“This paves the way for using these molecules as new therapeutic targets and disease markers at very early stages when cancer is much more likely to be cured.”

The study compared neonatal blood tests and Guthrie cards in infants with acute leukemia in infancy to children without blood disorders. They found that one particular circular RNA was present at much higher levels at birth, before the onset of leukemia symptoms.

The results of this study suggest that the abundance of circular RNA molecules in the cells of certain individuals is a major determinant of why these particular oncogenes or oncogenes develop and why others do not. suggests that

“Circular RNAs can bind to DNA at different locations in different cells. By binding to DNA at specific sites, these circular RNAs can cause a number of changes, ultimately leading to DNA breaks. But cells need to repair this DNA to survive,” says Professor Conn.

“This repair is not always perfect and can result in small mutations such as misspellings of words in a book or, worse, very large and devastating mutations.

“Circular RNA can also change the physical position of broken DNA in the cell nucleus, so that it sticks two different regions of DNA together during the repair process, much like tearing two different books apart and sticking them together. can do.”

Lead author Vanessa Kong, Ph.D., says that multiple circular RNAs appear to work in concert to cause breaks at multiple sites in the DNA.

“This process, called chromosomal translocation, is a big problem for cells because it actually causes gene fusions that transform cells from normal to cancerous,” she says.

“This was demonstrated in two different cell types, and we found that this drives the rapid onset of progressive leukemia.”

Gene fusions resulting from the action of these circular RNAs are at well-known mutational ‘hotspots’ in blood cancer leukemias. This is an important consideration in Australia, which has the highest incidence of leukemia in the world and currently has approximately 35,000 Australians living with the disease.

These gene fusions have been used for years by physicians around the world to guide treatment options because they are known to worsen the prognosis of patients with them, the researchers say. .

However, until now it was unclear how these mutations arose, even though more than 100 known fusions have been found in patients.

“Of course, the ER3D process is not unique to leukemia,” says Dr. Conn.

“We now have evidence that ER3D is not restricted to leukemia but also has implications for other cancers and human diseases,” she says.

Researchers at Flinders University continue their work investigating the role of circular RNA in cancer and other diseases.

article, Circular RNA promotes oncogenic chromosomal translocations within the MLL recombinome in leukemia (2023) by VM Conn, M Gabryelska, J Toubia, K Kirk, L Gantley, JA Powell, G Cildir, S Marri, R Liu, BW Stringer, S Townley, ST Webb, H Lin, SE Samaraweera, S Bailey, AS Moore, M Maybury, D Liu, AD Collella, T Chataway, CT Wallington-Gates, L Walters, J Sibbons, LA Selth, V Tergaonkar, RJ D’Andrea, SM Pitson, GJ Goodall, SJ Conn have been published. cancer cell DOI: 10.1016/j.ccell.2023.05.002

https://doi.org/10.1016/j.ccell.2023.05.002

Research groups from Flinders University, University of South Australia, University of Adelaide, SA Pathology, University of Queensland, Children’s Health Queensland Hospital and Health Service, and A*STAR (Singapore) participated in this study.