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

Caryn S Ross-Innes, Jennifer Becq, Andrew Warren, R Keira Cheetham, Helen Northen, Maria O'Donovan, Shalini Malhotra, Massimiliano di Pietro, Sergii Ivakhno, Miao He, Jamie M J Weaver, Andy G Lynch, Zoya Kingsbury, Mark Ross, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group, John O'Neill (Member of Group Organisation), Richard Skipworth (Member of Group Organisation), Sean Humphray, David Bentley, Rebecca C Fitzgerald

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1038-46
Number of pages9
JournalNature Genetics
Volume47
Issue number9
Early online date20 Jul 2015
DOIs
Publication statusPublished - Sep 2015

Fingerprint

Dive into the research topics of 'Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma'. Together they form a unique fingerprint.

Cite this