Training Programme in Translational Medicine and Therapeutics at the University of Cambridge: 'Comprehensive analysis of structural rearrangements in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.' (360G-Wellcome-095224_Z_11_Z)

Oesophageal adenocarcinoma has a dismal prognosis; median survival is < 1 year. It is thought that chromosomal rearrangements (including inversions, translocations, deletions and insertions) may play as much of a role in the development of cancer as the more thoroughly studied point mutations. Paired-end Sequencing allows rapid analysis of virtually all breakpoints in a tumour to a resolution of 500bp. Simultaneously it provides highly accurate copy number data comparable to that from arrayCGH. The Barrett's-?Dysplasia-?OAC is a well recognised paradigm. Ease of accessibility and longitudinal sampling as part of standard clinical practice provides a unique opportunity to study the biology of progression in epithelial carcinoma. Key Goals 1. Investigate structural rearrangements and copy number abnormalities involved in the genesis of oesophageal carcinoma in a small group of carefully selected patients with samples representing Barrett's oesophagus, Oesophageal adenocarcinoma and normal tissue from the same patient. 2. Confirm the importance of individual structural rearrangements by screening a large collection of primary tissue samples and comparison with clinical outcome 3. Functional assessment of potential therapeutic targets 4. Investigate the potential of personalised assays, based on unique structural rearrangements, for tumour cell-free DNA in patient serum as markers of disease status