E-resources
Peer reviewed
Open access
-
Erwin, Graham S; Gürsoy, Gamze; Al-Abri, Rashid; Suriyaprakash, Ashwini; Dolzhenko, Egor; Zhu, Kevin; Hoerner, Christian R; White, Shannon M; Ramirez, Lucia; Vadlakonda, Ananya; Vadlakonda, Alekhya; von Kraut, Konor; Park, Julia; Brannon, Charlotte M; Sumano, Daniel A; Kirtikar, Raushun A; Erwin, Alicia A; Metzner, Thomas J; Yuen, Ryan K C; Fan, Alice C; Leppert, John T; Eberle, Michael A; Gerstein, Mark; Snyder, Michael P
Nature (London), 01/2023, Volume: 613, Issue: 7942Journal Article
Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases . 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 cancer . 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.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.