Authors:
CS Ross-Innes, J Becq, A Warren, RK Cheetham, H Northen, M O'Donovan, S Malhotra, M di Pietro, S Ivakhno, M He, JMJ Weaver, AG Lynch, Z Kingsbury, M Ross, S Humphray, D Bentley, RC Fitzgerald
Journal name: 
Nat Genet
Citation info: 
47(9):1038-1046
Abstract: 
The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture.
DOI: 
http://doi.org/10.1038/ng.3357
Research group: 
Tavaré Group
E-pub date: 
01 Sep 2015