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

作者：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 N; Strefford Jonathan C; Rose Zerilli Matthew; Thomas Gareth J; Ang Yeng; Sharrocks Andrew D; Fitzgerald Rebecca C; Underwood Timothy J

来源：Scientific Reports, 2016, 6(1): 32417.

DOI：10.1038/srep32417

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.

• 出版日期2016-9-7