TY - JOUR
T1 - Authentication and characterisation of a new oesophageal adenocarcinoma cell line
T2 - MFD-1
AU - Garcia, Edwin
AU - Hayden, Annette
AU - Birts, Charles
AU - Britton, Edward
AU - Cowie, Andrew
AU - Pickard, Karen
AU - Mellone, Massimiliano
AU - Choh, Clarisa
AU - Derouet, Mathieu
AU - Duriez, Patrick
AU - Noble, Fergus
AU - White, Michael J.
AU - Primrose, John N.
AU - Strefford, Jonathan C.
AU - Rose-Zerilli, Matthew
AU - Thomas, Gareth J.
AU - Ang, Yeng
AU - Sharrocks, Andrew D.
AU - Fitzgerald, Rebecca C.
AU - Underwood, Timothy J.
AU - OCCAMS Consortium
AU - Lynch, Andy G.
PY - 2016/9/7
Y1 - 2016/9/7
N2 - 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.
AB - 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.
U2 - 10.1038/srep32417
DO - 10.1038/srep32417
M3 - Article
AN - SCOPUS:84987680020
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 32417
ER -