4.7 Article

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

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SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/srep32417

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资金

  1. Cancer Research UK for the OCCAMS/ICGC project
  2. MRC Clinician Scientist Grant
  3. NIHR Cambridge Biomedical Research Centre
  4. Addenbrooke's Hospital
  5. UCL
  6. MCRC CRUK clinical training fellowship
  7. MRC [MR/M008908/1, G1002565] Funding Source: UKRI
  8. Cancer Research UK [15874] Funding Source: researchfish
  9. Medical Research Council [G1002565, MR/M008908/1] Funding Source: researchfish
  10. Versus Arthritis
  11. Cancer Research UK [20406] Funding Source: researchfish

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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.

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