Details

Autor(en) / Beteiligte

• 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.

Titel

Recurrent repeat expansions in human cancer genomes

Ist Teil von

• Nature (London), 2023-01, Vol.613 (7942), p.96-102

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases 1 , 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 cancer 3 – 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. An atlas explores the landscape of recurrent repeat expansions in human cancer genomes.