| Autor: |
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, 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 |
| Rok vydání: |
2016 |
| 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 |
| Externí odkaz: |
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