Transcriptional immune suppression and upregulation of double stranded DNA damage and repair repertoires in ecDNA-containing tumors-Reference-Cited by-同舟云学术

Transcriptional immune suppression and upregulation of double stranded DNA damage and repair repertoires in ecDNA-containing tumors

Published:2023-08-10 Issue: Volume: Page:
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Author:

Lin Miin S.¹,Jo Se-Young²,Luebeck Jens³,Chang Howard Y.⁴⁵⁶,Wu Sihan⁷,Mischel Paul S.⁸⁹,Bafna Vineet³¹⁰

Affiliation:

1. Bioinformatics and Systems Biology Graduate Program, University of California at San Diego, La Jolla, CA, USA

2. Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea

3. Department of Computer Science and Engineering, University of California at San Diego, La Jolla, CA, USA

4. Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA

5. Department of Genetics, Stanford University, Stanford, CA, USA

6. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA

7. Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA

8. Sarafan Chemistry, Engineering, and Medicine for Human Health (Sarafan ChEM-H), Stanford University, Stanford, CA, USA

9. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

10. Halıcıoğlu Data Science Institute, University of California at San Diego, La Jolla, CA, USA

Abstract

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 upregulate DNA damage and repair, cell cycle control, and mitotic processes, but downregulate 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.

Publisher

eLife Sciences Publications, Ltd

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