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Nat Genet. 2015 Sep;47(9):1038-1046. doi: 10.1038/ng.3357. Epub 2015 Jul 20.

Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.

Author information

1
Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK.
2
Illumina, Chesterford Research Park, Little Chesterford, UK.
3
Department of Histopathology, Addenbrooke's Hospital, Cambridge, UK.
4
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
#
Contributed equally

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.

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PMID:
26192915
PMCID:
PMC4556068
DOI:
10.1038/ng.3357
[Indexed for MEDLINE]
Free PMC Article
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