ROME Therapeutics Announces Publication in Nature Communications of First Large-Scale, Pan-Cancer Analysis of LINE-1 Expression Levels and Retrotransposon Activity

• Data revealed high correlation between LINE-1 expression and retrotransposon (RT) burden, with variability across tumor types and genomic loci, demonstrating the potential for precision LINE-1 RT-targeted therapeutic approaches

/EIN News/ -- BOSTON, March 03, 2025 (GLOBE NEWSWIRE) -- ROME Therapeutics, a biotechnology company illuminating the intersection of the dark genome and innate immunity to develop breakthrough medicines for autoimmune and neurodegenerative diseases, today announced a publication in the journal Nature Communications that is believed to be the most comprehensive analysis of LINE-1 retrotransposon (RT) activity in cancer to date. ROME scientists collaborated with researchers at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, and Weill Cornell Medical College on the landmark computational research and paper entitled, “Pan-cancer multi-omic model of LINE-1 activity reveals locus heterogeneity of retrotransposition efficiency.” (Link to paper here.)

A highly prevalent repetitive element in the dark genome, LINE-1 is typically silenced, but can be activated under cellular stress and pathologic conditions. Emerging research implicates LINE-1’s aberrant activity across a range of therapeutic areas and diseases. In cancer, LINE-1 is often dysregulated, resulting in increased production of disease-driving proteins. LINE-1 can also retrotranspose (or reinsert itself into new locations on chromosomes, known as loci) in the nucleus, causing genomic instability, which is also a hallmark of cancer.

“We’re extremely proud of this paper, as it further demonstrates ROME’s pioneering leadership in understanding the role LINE-1 RT plays in human disease, as well as our commitment to harnessing cutting-edge computation to guide therapeutic innovation,” said Heike Keilhack, Ph.D., Chief Scientific Officer at ROME Therapeutics. “While our current internal focus at ROME is on advancing medicines to inhibit LINE-1 RT’s pathogenic activity in autoimmune and neurodegenerative diseases, we believe the data published in Nature Communications will spur broader, deeper research into LINE-1 RT’s cancer-driving activity and, ultimately, inspire novel cancer therapies to address unmet patient needs.”

ROME scientists and their collaborators analyzed a recently updated data set released from The Cancer Genome Atlas (TCGA) comprising nearly 5,000 pan-cancer paired tumor-normal whole-genome sequencing samples and approximately 9,000 tumor RNA samples. The researchers developed an improved algorithm for detecting LINE-1 retrotransposition events, TotalReCall (publicly available here), which they used to characterize LINE-1 DNA insertions alongside RNA expression, finding high correlation between LINE-1 expression and RT burden. The analyses revealed significant variability in LINE-1 activity across tumor types and across different LINE-1 loci across the genome. In particular, this research demonstrated, at scale, what has been previously shown in vitro for only a small number of elements: that different LINE-1 elements are capable of variable RT activity. This genomic heterogeneity of LINE-1 among cancer patients suggests the potential for novel precision therapeutic approaches.

Benjamin Greenbaum, Ph.D., Associate Attending, Computational Oncologist in the Division of Computational Oncology at Memorial Sloan Kettering Cancer Center, a corresponding author on the paper, commented, “The dark genome presents a unique biological challenge in that its vastness translates to a massive amount of data that far exceeds the complexity of the exome. As demonstrated by these data, we now have the computational firepower and know-how to catalog and analyze LINE-1 and other dark genome elements. This research is a vital step in elucidating pathogenic implications of LINE-1 RT in various tumor types and, importantly, laying the groundwork to discover and develop new, personalized approaches that are key to maximizing therapeutic outcomes in cancer patients.”

Dr. Greenbaum has financial interests related to ROME Therapeutics.

About ROME

ROME Therapeutics is a pioneer and leader in illuminating the intersection of the dark genome and innate immunity to develop breakthrough medicines for autoimmune and neurodegenerative diseases. The company integrates data science, biology, chemistry and translational capabilities to understand and drug repetitive elements in the dark genome such as LINE-1 to advance a pipeline of medicines with the potential to treat underlying causes of disease. ROME’s lead program, a LINE-1 RT inhibitor for Type 1 interferonopathies, has the potential to be the first non-immunosuppressant treatment for autoimmune diseases. ROME is based in Boston, Mass. For more information, please visit www.rometx.com.

Media Contact

Liz Melone
Melone Communications
liz@melonecomm.com