New biological tools are required to understand the functional significance of genetic events revealed
by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell
line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic
genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6.
WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC
cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in
MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high
SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four
somatically acquired mutations in three recurrent mutated genes in OAC: TP53, ABCB1 and SEMA5A,
not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and
a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and
invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using
accurate model systems to develop molecular-phenotype therapeutics. We have described the first such
system to arise from the oesophageal International Cancer Genome Consortium project
