Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1

Edwin Garcia, Annette Hayden, Charles Birts, Edward Britton, Andrew Cowie, Karen Pickard, Massimiliano Mellone, Clarisa Choh, Mathieu Derouet, Patrick Duriez, Fergus Noble, Michael J. White, John N. Primrose, Jonathan C. Strefford, Matthew Rose-Zerilli, Gareth J. Thomas, Yeng Ang, Andrew D. Sharrocks, Rebecca C. Fitzgerald, Timothy J. Underwood*OCCAMS Consortium

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Article number32417
Number of pages12
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 7 Sept 2016

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