Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas.
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Authors
Contino, Gianmarco
Killcoyne, Sarah
Hsu, Ray
Abbas, Sujath
Su, Jing
Redmond, Aisling M
Weaver, Jamie MJ
Tavaré, Simon
Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium
Publication Date
2022-04-08Journal Title
Commun Biol
ISSN
2399-3642
Publisher
Springer Science and Business Media LLC
Volume
5
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Ng, A. W. T., Contino, G., Killcoyne, S., Devonshire, G., Hsu, R., Abbas, S., Su, J., et al. (2022). Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas.. Commun Biol, 5 (1) https://doi.org/10.1038/s42003-022-03238-7
Abstract
Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies.
Keywords
Humans, Adenocarcinoma, Esophageal Neoplasms, Genome, Human, Histone Acetyltransferases, Whole Genome Sequencing
Sponsorship
National Institute for Health Research (IS-BRC-1215-20014)
Identifiers
35396535, PMC8993906
External DOI: https://doi.org/10.1038/s42003-022-03238-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336962
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