Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression

Thomas G. Paulson (), Patricia C. Galipeau, Kenji M. Oman, Carissa A. Sanchez, Mary K. Kuhner, Lucian P. Smith, Kevin Hadi, Minita Shah, Kanika Arora, Jennifer Shelton, Molly Johnson, Andre Corvelo, Carlo C. Maley, Xiaotong Yao, Rashesh Sanghvi, Elisa Venturini, Anne-Katrin Emde, Benjamin Hubert, Marcin Imielinski, Nicolas Robine, Brian J. Reid and Xiaohong Li ()
Additional contact information
Thomas G. Paulson: Fred Hutchinson Cancer Research Center
Patricia C. Galipeau: Fred Hutchinson Cancer Research Center
Kenji M. Oman: Fred Hutchinson Cancer Research Center
Carissa A. Sanchez: Fred Hutchinson Cancer Research Center
Mary K. Kuhner: University of Washington
Lucian P. Smith: University of Washington
Kevin Hadi: New York Genome Center (NYGC)
Minita Shah: New York Genome Center (NYGC)
Kanika Arora: New York Genome Center (NYGC)
Jennifer Shelton: New York Genome Center (NYGC)
Molly Johnson: New York Genome Center (NYGC)
Andre Corvelo: New York Genome Center (NYGC)
Carlo C. Maley: Arizona State University
Xiaotong Yao: New York Genome Center (NYGC)
Rashesh Sanghvi: New York Genome Center (NYGC)
Elisa Venturini: New York Genome Center (NYGC)
Anne-Katrin Emde: Variant Bio
Benjamin Hubert: New York Genome Center (NYGC)
Marcin Imielinski: New York Genome Center (NYGC)
Nicolas Robine: New York Genome Center (NYGC)
Brian J. Reid: Fred Hutchinson Cancer Research Center
Xiaohong Li: Fred Hutchinson Cancer Research Center

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract While the genomes of normal tissues undergo dynamic changes over time, little is understood about the temporal-spatial dynamics of genomes in premalignant tissues that progress to cancer compared to those that remain cancer-free. Here we use whole genome sequencing to contrast genomic alterations in 427 longitudinal samples from 40 patients with stable Barrett’s esophagus compared to 40 Barrett’s patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett’s tissue regardless of outcome, with high levels of mutation, ESAD gene and focal chromosomal alterations, and similar mutational signatures. The critical distinction between stable Barrett’s versus those who progress to cancer is acquisition and expansion of TP53−/− cell populations having complex structural variants and high-level amplifications, which are detectable up to six years prior to a cancer diagnosis. These findings reveal the timing of common somatic genome dynamics in stable Barrett’s esophagus and define key genomic features specific to progression to esophageal adenocarcinoma, both of which are critical for cancer prevention and early detection strategies.

Date: 2022
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DOI: 10.1038/s41467-022-29767-7

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