Whole methylome changes in Barrett's metaplasia, dysplasia, and cancer
- 1CSIRO
Abstract
The clinical management of Barrett's esophagus (BE) and the risk of esophageal adenocarcinoma (EAC) is dependent on the presence or absence of dysplasia. The histopathological diagnosis of dysplasia is unreliable however, and would benefit from additional diagnostic criteria. Here, we obtained EM-seq whole-genome methylation profiles from 86 samples across the BE/EAC disease spectrum, notably supplementing the scant existing methylation evidence for low-grade and high-grade dysplasia. While the bulk of methylation changes occur in the transition from normal squamous epithelium to intestinal metaplasia (non-dysplastic Barrett's esophagus), we identified a smaller set of changes that mark the onset of dysplasia and progression to EAC. Methylation changes were broadly independent of copy number variation. They were tightly anticorrelated with RNA-seq expression for some genes. Deconvolution of the bulk methylation signatures into constituent cell types revealed four sample groupings enriched with a particular cell type (squamous, columnar, lymphoid and erythroid cells), somewhat reflecting existing clinical classifications. We outline potential markers that could improve the diagnosis of metaplasia and dysplasia in EAC.
Related
- Detection of high-grade dysplasia and adenocarcinoma in Barrett's esophagus using high-resolution virtual chromoendoscopy versus the Seattle protocol: the CONVERSE study
- Optimising Expert Pathology Referral in Barrett's Oesophagus Dysplasia Through p53‐Guided Triage: A Nationwide Real‐World Cohort Study
- Protracted copy number alteration evolution in Barrett's oesophagus leading to oesophageal cancer
- Towards reliable morphological subtyping and cancer detection on Barrett's esophagus pathology through ensembling foundation models.
- Pan-cancer Graph-based Cancer Detection Using the Cell-free DNA Methylome
BibTeX
@misc{liew2026whole,
title = {{Whole methylome changes in Barrett's metaplasia, dysplasia, and cancer}},
author = {Y. J. Liew and T. Udumanne and K. Catalan and A. Ariyavidana and K. K. M. Lee-Ng and D. Pascovici and T. Yang and P. Kumarasinghe and D. McLeod and I. Brown and M. J. Bourke and S. J. Lord and R. V. Lord and J. Ross},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763255},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763255v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Whole methylome changes in Barrett's metaplasia, dysplasia, and cancer
AU - Y. J. Liew
AU - T. Udumanne
AU - K. Catalan
AU - A. Ariyavidana
AU - K. K. M. Lee-Ng
AU - D. Pascovici
AU - T. Yang
AU - P. Kumarasinghe
AU - D. McLeod
AU - I. Brown
AU - M. J. Bourke
AU - S. J. Lord
AU - R. V. Lord
AU - J. Ross
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763255
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763255v1
AB - The clinical management of Barrett's esophagus (BE) and the risk of esophageal adenocarcinoma (EAC) is dependent on the presence or absence of dysplasia. The histopathological diagnosis of dysplasia is unreliable however, and would benefit from additional diagnostic criteria. Here, we obtained EM-seq whole-genome methylation profiles from 86 samples across the BE/EAC disease spectrum, notably supplementing the scant existing methylation evidence for low-grade and high-grade dysplasia. While the bulk of methylation changes occur in the transition from normal squamous epithelium to intestinal metaplasia (non-dysplastic Barrett's esophagus), we identified a smaller set of changes that mark the onset of dysplasia and progression to EAC. Methylation changes were broadly independent of copy number variation. They were tightly anticorrelated with RNA-seq expression for some genes. Deconvolution of the bulk methylation signatures into constituent cell types revealed four sample groupings enriched with a particular cell type (squamous, columnar, lymphoid and erythroid cells), somewhat reflecting existing clinical classifications. We outline potential markers that could improve the diagnosis of metaplasia and dysplasia in EAC.
ER -