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

Scientific Reports2016Vol. 6(1), pp. 32417–32417

Citations Over TimeTop 11% of 2016 papers

Edwin Garcia, Annette Hayden, Charles N. Birts, Edward Britton, Andrew Cowie, Karen Pickard, Massimiliano Mellone, C Choh, Mathieu Derouet, Patrick J. Duriez, Fergus Noble, Michael J. White, John Primrose, Jonathan C. Strefford, Matthew Rose‐Zerilli, Gareth J. Thomas, Yeng Ang, Andrew D Sharrocks, Rebecca C. Fitzgerald, Tim Underwood, Shona MacRae, Nicola Grehan, Zarah Abdullahi, Rachel de la Rue, Ayesha Noorani, Rachael Fels Elliott, Nadeera de Silva, Jan Bornschein, Maria O’Donovan, Gianmarco Contino, Yeng Ang, Hamza Chettouh, Jason Crawte, Barbara Nutzinger, Paul A. Edwards, Laura Smith, Ahmad Miremadi, Shalini Malhotra, Alison D. Cluroe, Richard Hardwick, Jim Davies, Hugo Ford, David Gilligan, Peter Safranek, Andrew Hindmarsh, Vijayendran Sujendran, Nick Carroll, Richard Turkington, Stephen J. Hayes, Yeng Ang, Shaun R. Preston, Sarah Oakes, Izhar Bagwan, Vicki Save, Richard J. E. Skipworth, Ted R. Hupp, J. Robert O’Neill, Olga Tucker, Philippe Tanière, Jack Owsley, Charles Crichton, Christian Schusterreiter, Hugh Barr, Neil A. Shepherd, Oliver Old, Jesper Lagergren, James Gossage, Andrew G. Davies, Fuju Chang, Janine Zylstra, Grant Sanders, Richard Berrisford, Catherine Harden, David Bunting, Mike Lewis, Ed Cheong, Bhaskar Kumar, Simon L. Parsons, Irshad Soomro, Philip Kaye, John Saunders, Laurence Lovat, Rehan Haidry, Victor Eneh, Laszlo Igali, Ian Welch, Michael Scott, Shamila Sothi, Sari Suortamo, Suzy Lishman, Duncan Beardsmore, Charlotte Anderson, Mike L. Smith, Maria Secrier, Matthew Eldridge, Lawrence Bower, Achilleas Achilleos, Andy G. Lynch, Simon Tavaré

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.

Citations Over TimeTop 11% of 2016 papers

Abstract

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