1. Genomic copy number predicts esophageal cancer years before transformation
- Author
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Eleanor Gregson, Sarah Killcoyne, Rebecca C. Fitzgerald, Dan J. Woodcock, Sujath Abbas, Rachel de la Rue, Moritz Gerstung, Adrienn Blasko, Aikaterini Varanou Jenkins, David C. Wedge, Cassandra Kosmidou, Matthew D. Eldridge, Ahmad Miremadi, Wladyslaw Januszewicz, Fitzgerald, Rebecca [0000-0002-3434-3568], Eldridge, Matthew [0000-0002-5799-8911], Abbas, Sujath [0000-0002-2541-4969], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,DNA Copy Number Variations ,Esophageal Neoplasms ,Biopsy ,Aneuploidy ,Gene mutation ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Barrett Esophagus ,0302 clinical medicine ,Internal medicine ,Cancer screening ,Medicine ,Humans ,Esophagus ,Aged ,medicine.diagnostic_test ,Manchester Cancer Research Centre ,Whole Genome Sequencing ,business.industry ,Genome, Human ,ResearchInstitutes_Networks_Beacons/mcrc ,General Medicine ,Genomics ,Esophageal cancer ,Middle Aged ,medicine.disease ,Human genetics ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Histopathology ,Female ,business ,Precancerous Conditions - Abstract
Recent studies show that aneuploidy and driver gene mutations precede cancer diagnosis by many years1–4. 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 exemplar5. 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. Longitudinal molecular profiling of copy number alterations in patients with Barrett’s esophagus can identify patients at higher risk of developing esophageal cancer.
- Published
- 2020
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