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

  • the OCCAMS consortium
  • University of Southampton
  • University of Manchester
  • Northern Care Alliance NHS Group
  • Wrightington, Wigan and Leigh NHS Trust
  • University of Cambridge
  • Cambridge University Hospitals NHS Foundation Trust
  • University of Oxford
  • Queen's University Belfast
  • Royal Surrey County Hospital NHS Foundation Trust
  • Edinburgh Royal Infirmary
  • University of Edinburgh
  • University Hospitals Birmingham NHS Foundation Trust
  • University of Birmingham
  • University Hospital Southampton NHS Foundation Trust
  • Gloucestershire Hospitals NHS Foundation Trust
  • St Sharrocks’s Hospital
  • King's College London
  • Karolinska Institutet
  • University Hospitals Plymouth NHS Trust
  • Norfolk and Norwich University Hospitals NHS Foundation Trust
  • Nottingham University Hospitals NHS Trust
  • University College London
  • Norfolk and Waveney Cellular Pathology Network
  • Manchester University NHS Foundation Trust
  • University Hospitals Coventry and Warwickshire NHS Trust
  • North West Anglia NHS Foundation Trust
  • University Hospitals of North Midlands NHS Trust
  • Cancer Research UK Cambridge Institute

Zinātniskās darbības rezultāts: Devums žurnālamZinātniskais raksts (žurnālā)koleģiāli recenzēts

20 Atsauces (Scopus)

Kopsavilkums

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.

OriģinālvalodaAngļu
Raksta numurs32417
ŽurnālsScientific Reports
Sējums6
DOIs
Publikācijas statussPublicēts - 7 sept. 2016
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