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

Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1
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.
1-12
Garcia, Edwin
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Hayden, Annette
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Birts, Charles
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Britton, Edward
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Cowie, Andrew
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Pickard, Karen
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Mellone, Massimiliano
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Choh, Clarisa
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Derouet, Mathieu
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Duriez, Patrick
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Noble, Fergus
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White, Michael J.
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Primrose, John
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Strefford, Jonathan C.
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Rose-Zerilli, Matthew
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Thomas, Gareth
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Ang, Yeng
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Sharrocks, Andrew D.
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Fitzgerald, Rebecca C.
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Underwood, Timothy J.
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Garcia, Edwin
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Hayden, Annette
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Birts, Charles
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Britton, Edward
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Cowie, Andrew
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Pickard, Karen
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Mellone, Massimiliano
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Choh, Clarisa
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Derouet, Mathieu
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Duriez, Patrick
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Noble, Fergus
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White, Michael J.
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Primrose, John
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Strefford, Jonathan C.
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Rose-Zerilli, Matthew
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Thomas, Gareth
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Ang, Yeng
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Sharrocks, Andrew D.
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Fitzgerald, Rebecca C.
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Underwood, Timothy J.
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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, Strefford, Jonathan C., Rose-Zerilli, Matthew, Thomas, Gareth, Ang, Yeng, Sharrocks, Andrew D., Fitzgerald, Rebecca C. and Underwood, Timothy J. (2016) Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1. Scientific Reports, 6 (32417), 1-12. (doi:10.1038/srep32417). (PMID:27600491)

Record type: Article

Abstract

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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More information

Accepted/In Press date: 4 August 2016
e-pub ahead of print date: 7 September 2016
Published date: 7 September 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 400936
URI: http://eprints.soton.ac.uk/id/eprint/400936
PURE UUID: 25d61f5a-7cc6-4927-a549-4f9d1cc7a033
ORCID for Charles Birts: ORCID iD orcid.org/0000-0002-0368-8766
ORCID for Massimiliano Mellone: ORCID iD orcid.org/0000-0002-4964-9340
ORCID for Patrick Duriez: ORCID iD orcid.org/0000-0003-1814-2552
ORCID for John Primrose: ORCID iD orcid.org/0000-0002-2069-7605
ORCID for Jonathan C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881
ORCID for Matthew Rose-Zerilli: ORCID iD orcid.org/0000-0002-1064-5350
ORCID for Timothy J. Underwood: ORCID iD orcid.org/0000-0001-9455-2188

Catalogue record

Date deposited: 30 Sep 2016 09:10
Last modified: 15 Mar 2024 03:36

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Contributors

Author: Edwin Garcia
Author: Annette Hayden
Author: Charles Birts ORCID iD
Author: Edward Britton
Author: Andrew Cowie
Author: Karen Pickard
Author: Massimiliano Mellone ORCID iD
Author: Clarisa Choh
Author: Mathieu Derouet
Author: Patrick Duriez ORCID iD
Author: Fergus Noble
Author: Michael J. White
Author: John Primrose ORCID iD
Author: Gareth Thomas
Author: Yeng Ang
Author: Andrew D. Sharrocks
Author: Rebecca C. Fitzgerald

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