Research at the University of Sydney indicates that non-coding DNA, which makes up 98% of our genome and was previously considered "junk" - that is, lacking a defined or redundant function, may play a crucial role in the diagnosis and treatment of cancer. The study found mutations in these regions associated with 12 different types of cancer
Research at the University of Sydney indicates that non-coding DNA, which makes up 98% of our genome and was previously considered "junk" - that is, lacking a defined or redundant function, may play a crucial role in the diagnosis and treatment of cancer. The study found mutations in these regions associated with 12 different types of cancer. These mutations occur in sites that bind the CTCF protein, which are important for maintaining the three-dimensional structure of the genome. Abnormalities in these sites may contribute to the development of cancer. The findings point to a potential universal approach to cancer treatment that aims to treat these common mutations in a variety of cancers.
Researchers at the Garvan Institute used artificial intelligence to identify potential cancer-causing elements within the "junk" DNA regions, opening the way to innovative methods in diagnosis and treatment.
According to the study, non-coding DNA - which makes up 98% of our genome and does not contain instructions for making proteins - may be the key to new cancer diagnoses and treatments. The findings, published in the journal Nucleic Acids Research, reveal mutations in previously ignored regions of the genome, which may contribute to the formation and development of at least 12 different types of cancer, including prostate, breast and colon cancer.
This discovery may lead to early diagnosis and new treatments that will be effective for a variety of cancers.
"Non-coding DNA was previously considered 'junk' due to the lack of a clear function," says Dr. Amanda Khoury, who heads the research at the Garvan Institute and co-author of the paper. "Our research found mutations in these regions of the DNA that could develop a completely new universal approach to cancer treatment."
Studying the anchors of cancer mutations in DNA
The researchers focused on mutations that affect binding sites for a protein called CTCF, which helps fold long strands of DNA into specific shapes. In their previous work, they found that these binding sites bring distant parts of the DNA closer together, creating three-dimensional structures that control which genes are turned on or off.
"We have already identified a subset of CTCF binding sites that are 'persistent' - that is, they act like anchors in the genome, and are found in different cell types," says Dr. Khoury. "We hypothesized that if these anchors become defective, it can disrupt the normal 3D organization of the genome and cause cancer."
To test this, the researchers developed a new and advanced machine learning (AI) tool called CTCF-INSITE, which used genomic and epigenomic features to predict which CTCF sites might be anchors that appear regularly in 12 types of cancer. They examined more than 3000 tumor samples from patients diagnosed with the 12 types of cancer, available from the International Genomic Consortium database, and found that the anchors that appear regularly are rich in mutations.
A universal approach to cancer treatment
The findings may have broad implications for the understanding and treatment of many types of cancer. "Most new cancer treatments must be carefully targeted to specific mutations that are not always common between different tumor types, but because these CTCF anchors are knocked down in a variety of cancers, we open up the possibility of developing approaches that could be effective for multiple cancers," says Professor Susan Clark, Head of the Cancer Epigenetics Laboratory at the Garvan Institute and lead author of the article.
The researchers are now planning further large-scale experiments using CRISPR gene editing to investigate how these anchor mutations disrupt the 3D genome and potentially cause cancer development.
"Now that we have discovered what we believe to be critical anchors of the genome and shown that they are important for maintaining the homeostasis of the genome structure, it makes sense that these non-coding DNA mutations would disrupt this homeostasis in the cancer cell - a hypothesis we will test when we edit them," says Professor Clark. "By observing the downstream effects, we hope to identify key genes or gene pathways affected by the mutations, which can be used as markers for the early detection of cancer or as targets for new treatments."
"Finding these clues that were hidden in a huge amount of data is a significant example) of the way in which artificial intelligence advances medical research," she says. "This is a completely new field in cancer research, and we are excited to continue to explore it further"
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