Recurrent repeat expansions in human cancer genomes

Graham S. Erwin (), Gamze Gürsoy, Rashid Al-Abri, Ashwini Suriyaprakash, Egor Dolzhenko, Kevin Zhu, Christian R. Hoerner, Shannon M. White, Lucia Ramirez, Ananya Vadlakonda, Alekhya Vadlakonda, Konor von Kraut, Julia Park, Charlotte M. Brannon, Daniel A. Sumano, Raushun A. Kirtikar, Alicia A. Erwin, Thomas J. Metzner, Ryan K. C. Yuen, Alice C. Fan, John T. Leppert, Michael A. Eberle, Mark Gerstein () and Michael P. Snyder ()
Additional contact information
Graham S. Erwin: Stanford University
Gamze Gürsoy: Columbia University
Rashid Al-Abri: Stanford University
Ashwini Suriyaprakash: Stanford University
Egor Dolzhenko: Illumina, Inc.
Kevin Zhu: Stanford University
Christian R. Hoerner: Stanford University School of Medicine
Shannon M. White: Stanford University
Lucia Ramirez: Stanford University
Ananya Vadlakonda: Stanford University
Alekhya Vadlakonda: Stanford University
Konor von Kraut: Stanford University
Julia Park: Stanford University
Charlotte M. Brannon: Stanford University
Daniel A. Sumano: Stanford University
Raushun A. Kirtikar: Stanford University
Alicia A. Erwin: Northwestern University
Thomas J. Metzner: Stanford University School of Medicine
Ryan K. C. Yuen: Genetics and Genome Biology, The Hospital for Sick Children
Alice C. Fan: Stanford University School of Medicine
John T. Leppert: Stanford University School of Medicine
Michael A. Eberle: Illumina, Inc.
Mark Gerstein: Yale University
Michael P. Snyder: Stanford University

Nature, 2023, vol. 613, issue 7942, 96-102

Abstract: Abstract Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases1,2. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer3–8. Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05515-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:613:y:2023:i:7942:d:10.1038_s41586-022-05515-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-05515-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().