Viral Mimicry in DNA Repeats Offers Clues for Cancer Therapy

A study published in Cell Genomics reveals a surprising role for parts of DNA once considered junk. These repetitive DNA sequences, or repeats, may actually mimic patterns found in pathogens, giving the immune system clues about potential threats. This discovery offers insights into how the human genome interacts with the immune system and how it may have evolved over time.

DNA contains many repetitive sequences, often dismissed as leftover genetic material with no real function. Šulc’s team found that some of these repeats resemble pathogen-associated molecular patterns (PAMPs), which are molecules commonly found on bacteria, viruses, and other microbes. Pattern recognition receptors (PRRs) of the immune system detect these PAMPs to trigger inflammation, a key part of the body’s defense against infection.

“Repetitive DNA sequences compose over half of the human genome and are often derived from integrated viruses and genetic parasites, including transposable elements [TEs],” the researchers explained. “In healthy cells, these sequences are normally inactive or transcriptionally silenced by epigenetic mechanisms, but, in certain diseases, they can become derepressed and transcribed.”

The researchers used advanced computational models to compare DNA sequences across multiple species. They found that certain repetitive sequences share structural and sequence features with PAMPs, suggesting that these repeats may act as molecular mimics to influence how the immune system detects potential threats.

“Being able to quantify mimicry, to have good methods for assessing what turns it on or off, is going to help us understand how the innate immune system interacts with cells and impacts their evolution, including during cancer evolution,” Benjamin Greenbaum, PhD, computational oncologist at Memorial Sloan Kettering Cancer Center, said in a news release.

This finding challenges the long-standing idea that repetitive DNA is useless. Instead, it hints that these sequences may have evolved for a reason. Understanding this could have important implications for health. For example, if the immune system mistakes these repeats for real pathogens, it might trigger unnecessary inflammation or contribute to autoimmune diseases.

This research opens up new avenues for cancer studies. Could repetitive DNA sequences be targeted to enhance the immune system’s ability to recognize and attack tumors? Might these repeats help explain why some cancers evade immune detection or why certain patients respond better to immunotherapy? By uncovering these hidden signals in our genome, scientists are gaining a deeper understanding of how DNA shapes immune surveillance in cancer.

“A better understanding of what activates the innate immune system can help us figure out how to improve immunotherapies,” Greenbaum said. “With cancer vaccines, it could help us learn how to make the vaccines more or less visible to the immune system so that we can better tune immune engagement.”

REFERENCES

1. Šulc P, Di Gioacchino A, Solovyov A, et al. Repeats mimic pathogen-associated patterns across a vast evolutionary landscape. Cell Genomics. September 24, 2025. DOI: 10.1016/j.xgen.2025.101011 External Link

2. New research helps model how the immune system shapes cancer development. News Release. October 7, 2025. Accessed October 9, 2025. https://www.eurekalert.org/news-releases/1101035