Does radiofrequency ablation of the lower oesophagus allow for clonal expansion of highly mutated neosquamous epithelium?

Abstract

Objective In Barrett’s oesophagus (BE), after radiofrequency ablation (RFA), the oesophagus can be repopulated with a stratified ‘neosquamous epithelium’ (NeoSE). While histologically normal, the origin and clonal make-up of this NeoSE is unknown. An increased understanding of NeoSE is important as some studies suggest that NeoSE is biologically abnormal. The aim of this study was to determine whether there were major differences in the mutational landscape or clonal size in NeoSE versus normal squamous epithelium and determine whether NeoSE shares any pathogenic mutations with BE.Methods and analysis 10 patients who underwent RFA and 10 samples from 8 control patients were sequenced using a clinical targeted sequencing platform (cohort 1). An additional, eight patients with paired preablation BE and postablation NeoSE were also sequenced (cohort 2). Patient advocates will be used to disseminate the findings of this study.Results NeoSE samples had a mean of 2.2 pathogenic mutations per sample, including 50% of samples with an NOTCH1 and 30% of samples with a TP53 mutation. The normal oesophagus samples had 1.5 mutations per sample, including 40% of samples with NOTCH1 and 10% of samples with TP53 mutations. There was no difference in mutational allele fractions between NeoSE and normal squamous samples. When we compared paired BE and NeoSE samples, no shared mutations were identified.Conclusion While there was a trend for more TP53 mutations in NeoSE, overall, the mutational profile and clonal sizes (allele fractions) were very similar, suggesting NeoSE is genomically similar to the normal oesophageal squamous epithelium.