Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1
Autor: | Garcia, Edwin, Hayden, Annette, Birts, Charles, Britton, Edward, Cowie, Andrew, Pickard, Karen, Mellone, Massimiliano, Choh, Clarisa, Derouet, Mathieu, Duriez, Patrick, Noble, Fergus, White, Michael J., Primrose, John N., Strefford, Jonathan C., Rose-Zerilli, Matthew, Thomas, Gareth J., Ang, Yeng, Sharrocks, Andrew D., Fitzgerald, Rebecca C., Underwood, Timothy J. |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: | |
Zdroj: | Garcia, E, Hayden, A, Birts, C, Britton, E, Cowie, A, Pickard, K, Mellone, M, Choh, C, Derouet, M, Duriez, P, Noble, F, White, M J, Primrose, J N, Strefford, J C, Rose-Zerilli, M, Thomas, G J, Ang, Y, Sharrocks, A D, Fitzgerald, R C & Underwood, T J 2016, ' Authentication and characterisation of a new oesophageal adenocarcinoma cell line : MFD-1 ', Scientific Reports, vol. 6, 32417 . https://doi.org/10.1038/srep32417 Scientific Reports |
DOI: | 10.1038/srep32417 |
Popis: | 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. |
Databáze: | OpenAIRE |
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