Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, United States
Se-Young Jo
Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
Jens Luebeck
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, United States
Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United States
Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, United States
Paul S Mischel
Sarafan Chemistry, Engineering, and Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, United States; Department of Pathology, Stanford University School of Medicine, Stanford, United States
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, United States; Halıcıoğlu Data Science Institute, University of California, San Diego, La Jolla, United States
Extrachromosomal DNA is a common cause of oncogene amplification in cancer. The non-chromosomal inheritance of ecDNA enables tumors to rapidly evolve, contributing to treatment resistance and poor outcome for patients. The transcriptional context in which ecDNAs arise and progress, including chromosomally-driven transcription, is incompletely understood. We examined gene expression patterns of 870 tumors of varied histological types, to identify transcriptional correlates of ecDNA. Here, we show that ecDNA-containing tumors impact four major biological processes. Specifically, ecDNA-containing tumors up-regulate DNA damage and repair, cell cycle control, and mitotic processes, but down-regulate global immune regulation pathways. Taken together, these results suggest profound alterations in gene regulation in ecDNA-containing tumors, shedding light on molecular processes that give rise to their development and progression.
