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Genomic copy number predicts esophageal cancer years before transformation
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Abstract
Recent studies show that aneuploidy and driver gene mutations precede cancer diagnosis by many years 1-4. We assess whether these genomic signals can be used for early detection and pre-emptive cancer treatment using the neoplastic precursor lesion Barrett's esophagus as an exemplar 5. Shallow whole-genome sequencing of 777 biopsies, sampled from 88 patients in Barrett's esophagus surveillance over a period of up to 15 years, shows that genomic signals can distinguish progressive from stable disease even 10 years before histopathological transformation. These findings are validated on two independent cohorts of 76 and 248 patients. These methods are low-cost and applicable to standard clinical biopsy samples. Compared with current management guidelines based on histopathology and clinical presentation, genomic classification enables earlier treatment for high-risk patients as well as reduction of unnecessary treatment and monitoring for patients who are unlikely to develop cancer.
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“In the context of MGUS and SMM, these translocations still associate with high-risk genomic features,59,97,98 but strangely do not always predict progression as one might expect.9,90,99”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [99]
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Metadata
- Authors
- Killcoyne, S., Gregson, E., Wedge, D. C., Woodcock, D. J., Eldridge, M. D., de la Rue, R., Miremadi, A., Abbas, S., Blasko, A., Kosmidou, C., Januszewicz, W., Jenkins, A. V., Gerstung, M., & Fitzgerald, R. C.
- Affiliations
- European Bioinformatics Institute (GB)
- University of Cambridge (GB)
- University of Manchester (GB)
- University of Oxford (GB)
- Cancer Research UK (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Gerstung, Moritz
- Fitzgerald, Rebecca C.
- ORCID
- Venue
- Nature Medicine
- Published
- 2020-09-07
- Volume
- 26
- Issue
- 11
- Pages
- 1726-1732
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC7116403
- OpenAlex
- W3083497411
- Cited by
- 149
- References
- 52
- Citations by year
- 2026: 16 · 2025: 26 · 2024: 24 · 2023: 27 · 2022: 20 · 2021: 32 · 2020: 3
- FWCI
- 18.73
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- United European Gastroenterology Research Prize, RG76026
- Topics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Barrett's esophagus, esophageal adenocarcinoma, cancer transformation, copy number alterations, early cancer detection, aneuploidy, genomic classification, cancer surveillance, preemptive therapy
- MeSH terms
- Whole Genome Sequencing, Aged, Aneuploidy, Barrett Esophagus, Biopsy, Esophageal Neoplasms, Female, Humans, Male, Middle Aged, Precancerous Conditions, Genome, Human, Genomics, DNA Copy Number Variations
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