Irvine, CA – November 12, 2020 – A new study, led by researchers from the University of California, Irvine, has deepened the understanding of epigenetic mechanisms in tumorigenesis and revealed a previously undetected repertoire of cancer driver genes. The study was published this week in Science Advances.
Using a new prediction algorithm, called DORGE (Discovery of Oncogenes and tumor suppressoR genes using Genetic and Epigenetic features), researchers were able to identify novel tumor suppressor genes (TSGs) and oncogenes (OGs), particularly those with rare mutations, by integrating the most comprehensive collection of genetic and epigenetic data.
“Existing bioinformatics algorithms do not sufficiently leverage epigenetic features to predict cancer driver genes, despite the fact that epigenetic alterations are known to be associated with cancer driver genes,” said senior author Wei Li, PhD, the Grace B. Bell chair and professor of bioinformatics in the
Department of Biological Chemistry at the UCI School of Medicine. “Our computational algorithm integrates public data on epigenetic and genetic alternations, to improve the prediction of cancer driver genes.”
Cancer results from an accumulation of key genetic alterations that disrupt the balance between cell division and apoptosis. Genes with “driver” mutations that affect cancer progression are known as cancer driver genes, and can be classified as TSGs and oncogenes OGs based on their roles in cancer progression.
This study demonstrated how cancer driver genes, predicted by DORGE, included both known cancer driver genes and novel driver genes not reported in current literature. In addition, researchers found that the novel dual-functional genes, which DORGE predicted as both TSGs and OGs, are highly enriched at hubs in protein-protein interaction (PPI) and drug/compound-gene networks.
“Our DORGE algorithm, successfully leveraged public data to discover the genetic and epigenetic alterations that play significant roles in cancer driver gene dysregulation,” explained Li. “These findings could be instrumental in improving cancer prevention, diagnosis and treatment efforts in the future.”
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This work was supported by grants from the National Institutes of Health, National Science Foundation, Sloan Research Fellowship, Johnson & Johnson WiSTEM2D Award, W. M. Keck Foundation Junior Faculty Award, and the Cancer Prevention and Research Institute of Texas-Baylor, College of Medicine Comprehensive Cancer Training Program.
About the UCI School of Medicine
Each year, the UCI School of Medicine educates more than 400 medical students, and nearly 150 doctoral and master’s students. More than 700 residents and fellows are trained at UCI Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master’s degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master’s in public health, or an MD/master’s degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.
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