title: Genetic progression of Barrett's oesophagus to oesophageal adenocarcinoma.
abstract: Barrett's oesophagus (BE) is the premalignant condition associated with the development of oesophageal adenocarcinoma (OAC). Diagnostically, p53 immunohistochemistry remains the only biomarker recommended clinically to aid histopathological diagnosis. The emerging mutational profile of BE is one of highly heterogeneous lesions at the genomic level with many mutations already occurring in non-dysplastic tissue. As well as point mutations, larger scale copy-number changes appear to have a key role in the progression to OAC and clinically applicable assays for the reliable detection of aneuploidy will be important to incorporate into future clinical management of patients. For some patients, the transition to malignancy may occur rapidly through a genome-doubling event or chromosomal catastrophe, termed chromothripsis, and detecting these patients may prove especially difficult. Given the heterogeneous nature of this disease, sampling methods to overcome inherent bias from endoscopic biopsies coupled with the development of more objective biomarkers than the current reliance on histopathology will be required for risk stratification. The aim of this approach will be to spare low-risk patients unnecessary procedures, as well as to provide endoscopic therapy to the patients at highest risk, thereby avoiding the burden of incurable metastatic disease.
authors.affiliation: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Biomedical Campus, Cambridge CB2 0XZ, UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Gregson
authors.affiliation: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Biomedical Campus, Cambridge CB2 0XZ, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Bornschein
authors.affiliation: MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Biomedical Campus, Cambridge CB2 0XZ, UK.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fitzgerald
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000782:Aneuploidy; D001471:Barrett Esophagus / Q000235:genetics*; D000072837:Chromothripsis; D056915:DNA Copy Number Variations / Q000235:genetics*; D004268:DNA-Binding Proteins; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009218:Myosins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics*; D039961:Semaphorins; D051901:Smad4 Protein / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; C500982:MYO18B protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C491228:SEMA5A protein, human; C497796:SMAD4 protein, human; D039961:Semaphorins; D051901:Smad4 Protein; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D009218:Myosins