Genomic copy number instability predicted the risk of disease progression among patients with Barrett esophagus years beforehand, showed a retrospective study recently reported in Nature Medicine.

Study researchers developed a risk prediction model using a matched case–control discovery cohort of 88 patients with Barrett esophagus and 777 samples obtained by endoscopy during a 15-year surveillance period. Samples were evaluated using shallow whole-genome sequencing to identify genome-wide copy number instability.

In a validation cohort of 76 patients with 213 samples, the model classified 55% of samples from patients with stable disease as low risk and 77% of samples from patients whose disease progressed as high risk, which was “largely” independent of histopathology.

The model was also applied to a validation cohort of 248 patients with 1272 samples and revealed that patients whose disease progressed were classified as high risk independent of pathology.

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Further analysis of the samples revealed that among patients whose disease progressed, 50% of endoscopies yielded at least 1 high-risk sample 8 or more years before histopathological diagnosis, and 78% of endoscopies yielded at least 1 high-risk sample 1 to 2 years before histopathological diagnosis.

The study researchers noted that current diagnostic guidelines require only 1 dysplastic sample to recommend treatment for a patient.

When current treatment guidelines were applied to patients in the discovery cohort, study researchers found that at the second surveillance endoscopy, 54% of patients who eventually had disease progression would have had earlier intervention and 51% who had stable disease would have had less frequent endoscopies.

“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,” the study researchers concluded.


Killcoyne S, Gregson E, Wedge DC, et al. Genomic copy number predicts esophageal cancer years before transformation. Nat Med. Published online September 7, 2020. doi:10.1038/s41591-020-1033-y