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Institute researchers find new cancer driver in cells

Dr. Rendong Yang, head of the Computational Cancer Genomics lab at The Hormel Institute, University of Minnesota published breakthrough research on exitron splicing (EIS) and its role in cancer. Dr. Yang and team looked at a collection of all the gene readouts present in a cell across over 9,000 tumor patient samples to discover how EIS affects cancer growth.

Dr. Yang’s lab is unique at The Hormel Institute because his research uses computers to find answers to cancer. He develops algorithms, creates machine learning approaches, and uses large scale data analysis to discover how cancer works, new approaches to treatments, and better ways for patients to learn about their specific cancer.

Exitron splicing (EIS) is a biological process that can change the sequence of genes when genes are transcribed from DNA to RNA and therefore spark abnormal protein products. EIS is poorly characterized, but emerging evidence suggests a role for EIS in cancer. Through a systematic investigation of EIS across 33 cancers from 9,599 tumor transcriptomes, Dr. Yang and team discovered EIS affected 63% of human coding genes and 95% of those events were tumor-specific.

“Notably, we observed a mutually exclusive pattern between EIS and cell mutations in their affected genes,” said Dr. Yang.

“This is important because it helps us understand what causes cancer to progress.  We discovered EIS altered known and new cancer driver genes for causing gain- or loss-of-function, which promotes tumor progression within the body. Our findings establish the importance of considering EIS alterations when nominating cancer driver events and newly formed antigens unrecognized by the immune system, which we called neoantigens.”

The comprehensive analysis of EIS events in cancer provides a reference of candidate cancer driver events, potential immunogenic neoantigens, and predictive signatures for immunotherapy response that are missed by genetic mutation analysis alone.

Going forward, Dr. Yang and team will build a database to annotate the newly detected tumor-specific EIS events for cancer patients who could be benefit from this resource to find potential new drug targets or predictive biomarkers of their immunotherapy treatment. In addition, the discovery of EIS-derived neoantigens that elicit the anti-tumor immune response could lead to the development of cancer vaccines or T-cell therapeutic strategies in treating advanced cases of hard-to-treat cancers.

Dr. Yang’s research paper “A pan-cancer transcriptome analysis of exitron splicing identifies novel cancer driver genes and neoepitopes” was published in Molecular Cell, a top journal in the molecular biology field. Dr. Ting-You Wang, the first author of the newly published research, is a postdoc in Dr. Yang’s lab and an Eagles Cancer Telethon Postdoctoral Fellow. Dr. Scott Dehm, Masonic Cancer Center collaborator, Dr. Yanan Ren, a member of the Computational Cancer Genomics lab, Dr. Luke Hoeppner, head of the Cancer Biology lab at The Hormel Institute, and members of his lab also contributed to the research.