Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.
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.
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Edwin
E
Garcia
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Annette
A
Hayden
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Charles
C
Birts
Faculty of Biology, Medicine and Health, Oxford Road, University of Manchester, Manchester, M13 9PT, UK.
Edward
E
Britton
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Andrew
A
Cowie
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Karen
K
Pickard
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Massimiliano
M
Mellone
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Clarisa
C
Choh
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Mathieu
M
Derouet
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Patrick
P
Duriez
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Fergus
F
Noble
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Michael J
MJ
White
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
John N
JN
Primrose
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Jonathan C
JC
Strefford
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Matthew
M
Rose-Zerilli
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Gareth J
GJ
Thomas
Faculty of Biology, Medicine and Health, Oxford Road, University of Manchester, Manchester, M13 9PT, UK.
Yeng
Y
Ang
Faculty of Biology, Medicine and Health, Oxford Road, University of Manchester, Manchester, M13 9PT, UK.
Andrew D
AD
Sharrocks
MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge, CB2 0XZ United Kingdom.
Rebecca C
RC
Fitzgerald
Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block, Tremona Road, Southampton, SO16 6YD, United Kingdom.
Timothy J
TJ
Underwood
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence / Q000235:genetics; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype