• Medientyp: E-Artikel
  • Titel: Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1
  • Beteiligte: 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.; MacRae, Shona; Grehan, Nicola; Abdullahi, Zarah; de la Rue, Rachel; [...]
  • Erschienen: Springer Science and Business Media LLC, 2016
  • Erschienen in: Scientific Reports, 6 (2016) 1
  • Sprache: Englisch
  • DOI: 10.1038/srep32417
  • ISSN: 2045-2322
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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: <jats:italic>TP53</jats:italic>, <jats:italic>ABCB1</jats:italic> and <jats:italic>SEMA5A</jats:italic>, 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.</jats:p>
  • Zugangsstatus: Freier Zugang