Early detection of Barrett’s oesophagus and oesophageal adenocarcinoma using Oxford Nanopore long-read sequencing

Abstract

Oesophagal adenocarcinoma (EAC) has a poor five-year survival rate of <20%. Its precursor lesion, Barrett's oesophagus (BE), provides an ideal opportunity to detect and treat cancer transformation at an earlier stage. We sequenced BE biopsies and EAC tumours, using Oxford Nanopore long reads, to detect genetic alterations arising in early and late disease stages. We identified complex rearrangements and carried out de novo assembly of the extrachromosomal DNA (ecDNA) reads from BE and EAC. In the same sample with EAC and adjacent BE, we reconstructed an ecDNA harbouring the ERBB2 oncogene, associated with more severe disease and progression to EAC.