Whole methylome changes in Barrett's metaplasia, dysplasia, and cancer

Whole-genome EM-seq methylation profiling of 86 Barrett’s esophagus/esophageal adenocarcinoma samples identifies a smaller dysplasia-to-EAC methylation set beyond the metaplasia shift.

• Why it matters: Dysplasia grading in Barrett’s esophagus is unreliable, limiting risk stratification for esophageal adenocarcinoma and motivating additional diagnostic methylation criteria.
• What they did: The study generated EM-seq methylation profiles across the BE/EAC spectrum, adding evidence for low-grade and high-grade dysplasia, and assessed links to RNA-seq expression and copy number variation.
• The result: Methylation changes were largely independent of copy number variation, anticorrelated with RNA-seq expression for some genes, and deconvolution revealed four cell-type–enriched groupings, supporting candidate markers for metaplasia and dysplasia diagnosis.

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