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Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1
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srep32417.pdf | Published version | 2.28 MB | Adobe PDF | View/Open |
Title: | Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1 |
Authors: | Garcia, E Hayden, A Birts, C Britton, E Cowie, A Pickard, K Mellone, M Choh, C Derouet, M Duriez, P Noble, F White, MJ Primrose, JN Strefford, JC Rose-Zerilli, M Thomas, GJ Ang, Y Sharrocks, AD Fitzgerald, RC Underwood, TJ MacRae, S Grehan, N Abdullahi, Z De la Rue, R Noorani, A Elliott, RF De Silva, N Bornschein, J O’Donovan, M Contino, G Yang, T-P Chettouh, H Crawte, J Nutzinger, B Edwards, PAW Smith, L Miremadi, A Malhotra, S Cluroe, A Hardwick, R Davies, J Ford, H Gilligan, D Safranek, P Hindmarsh, A Sujendran, V Carroll, N Turkington, R Hayes, SJ Ang, Y Preston, SR Oakes, S Bagwan, I Save, V Skipworth, RJE Hupp, TR O’Neill, JR Tucker, O Taniere, P Owsley, J Crichton, C Schusterreiter, C Barr, H Shepherd, N Old, O Lagergren, J Gossage, J Davies, A Chang, F Zylstra, J Sanders, G Berrisford, R Harden, C Bunting, D Lewis, M Cheong, E Kumar, B Parsons, SL Soomro, I Kaye, P Saunders, J Lovat, L Haidry, R Eneh, V Igali, L Welch, I Scott, M Sothi, S Suortamo, S Lishman, S Beardsmore, D Anderson, C Smith, ML Secrier, M Eldridge, MD Bower, L Achilleos, A Lynch, AG Tavare, S |
Item Type: | Journal Article |
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. |
Issue Date: | 7-Sep-2016 |
Date of Acceptance: | 4-Aug-2016 |
URI: | http://hdl.handle.net/10044/1/42756 |
DOI: | https://dx.doi.org/10.1038/srep32417 |
ISSN: | 2045-2322 |
Publisher: | Nature Publishing Group |
Start Page: | 32417 |
End Page: | 32417 |
Journal / Book Title: | Scientific Reports |
Volume: | 6 |
Copyright Statement: | © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Publication Status: | Published |
Appears in Collections: | Physics Photonics Faculty of Natural Sciences |