Protracted copy number alteration evolution in Barrett's oesophagus leading to oesophageal cancer
- 1Institute of Cancer Research
Abstract
Detection of copy number alterations (CNAs) in Barretts oesophagus (BO) predicts oesophageal adenocarcinoma (OAC) risk. When CNAs first occur is unknown. Here we show that CNAs typically form in BO many decades prior to first clinical detection of BO or cancer, and often during childhood. Using a novel molecular clock analysis, we analysed spatiotemporal longitudinal whole genome data from 80 individuals within BO surveillance. Chr 9p loss of heterozygosity (LOH) tended to be the first CNA event typically occurring at age 10-30 years. Genome doubling (GD) also typically originated multiple decades prior to cancer develop. Patients who progressed to OAC had an enrichment of CNAs late in life. CNA rate was more predictive of cancer risk than CNA burden. Analysis of OAC whole genomes confirmed the early-life origins of cancer-associated CNAs. The malignant transformation potential of BO may be set during the first decades of life, enabling early cancer interception.
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BibTeX
@misc{gabbutt2026protracted,
title = {{Protracted copy number alteration evolution in Barrett's oesophagus leading to oesophageal cancer}},
author = {C. Gabbutt and A. Fernandez-Sanroman and H. Grant and S. Milite and W. C. Cross and N. A. Wright and C. C. Maley and A. Sottoriva and G. Caravagna and T. G. Paulson and T. A. Graham},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.26365037},
url = {https://www.medrxiv.org/content/10.64898/2026.10.16.26365037v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Protracted copy number alteration evolution in Barrett's oesophagus leading to oesophageal cancer
AU - C. Gabbutt
AU - A. Fernandez-Sanroman
AU - H. Grant
AU - S. Milite
AU - W. C. Cross
AU - N. A. Wright
AU - C. C. Maley
AU - A. Sottoriva
AU - G. Caravagna
AU - T. G. Paulson
AU - T. A. Graham
PY - 2026
DA - 2026/10/16
PB - medRxiv
DO - 10.64898/2026.10.16.26365037
UR - https://www.medrxiv.org/content/10.64898/2026.10.16.26365037v1
AB - Detection of copy number alterations (CNAs) in Barretts oesophagus (BO) predicts oesophageal adenocarcinoma (OAC) risk. When CNAs first occur is unknown. Here we show that CNAs typically form in BO many decades prior to first clinical detection of BO or cancer, and often during childhood. Using a novel molecular clock analysis, we analysed spatiotemporal longitudinal whole genome data from 80 individuals within BO surveillance. Chr 9p loss of heterozygosity (LOH) tended to be the first CNA event typically occurring at age 10-30 years. Genome doubling (GD) also typically originated multiple decades prior to cancer develop. Patients who progressed to OAC had an enrichment of CNAs late in life. CNA rate was more predictive of cancer risk than CNA burden. Analysis of OAC whole genomes confirmed the early-life origins of cancer-associated CNAs. The malignant transformation potential of BO may be set during the first decades of life, enabling early cancer interception.
ER -