@article{70639eb4fa7c408e9286986de7b542a9,
title = "Somatic whole genome dynamics of precancer in Barrett{\textquoteright}s esophagus reveals features associated with disease progression",
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{\textquoteright}s esophagus compared to 40 Barrett{\textquoteright}s patients who progressed to esophageal adenocarcinoma (ESAD). We show the same somatic mutational processes are active in Barrett{\textquoteright}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{\textquoteright}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{\textquoteright}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.",
author = "Paulson, {Thomas G.} and Galipeau, {Patricia C.} and Oman, {Kenji M.} and Sanchez, {Carissa A.} and Kuhner, {Mary K.} and Smith, {Lucian P.} and Kevin Hadi and Minita Shah and Kanika Arora and Jennifer Shelton and Molly Johnson and Andre Corvelo and Maley, {Carlo C.} and Xiaotong Yao and Rashesh Sanghvi and Elisa Venturini and Emde, {Anne Katrin} and Benjamin Hubert and Marcin Imielinski and Nicolas Robine and Reid, {Brian J.} and Xiaohong Li",
note = "Funding Information: This study was made possible by the lifelong commitment of Dr. Brian Reid to improving the lives of patients with Barrett?s esophagus. We thank all the research participants who have made this study possible. We thank and acknowledge the support of the following medical and research staff who provided clinical care of the Seattle Barrett?s Esophagus Program patients over the course of three decades and thus made this study possible: Dr. Douglas Levine, Dr. Peter Rabinovitch, Dr. Thomas Vaughan, Dr. Patricia Blount, Dr. Kamran Ayub, Dr. Shayan Irani, Dr. Michael Saunders, Dr. Rodger Haggitt, Dr. Robert Odze, Susan Irvine RN, Christine Karlsen, and Patricia Christopherson. David Cowan and Terri Watson provided database support. Tami Tolpa (Fig.?1), Pritha Chanana, Timothy Chu, and Michael Northup helped with figure preparation. Jon Yamato and Diego Mallo provided additional analytical support. Amber Karnofski provided administrative support. T.G.P, P.C.G., K.M.O, C.A.S., B.J.R., and X.L. were supported by NIH P01 CA91955 and P30 CA015704. M.K.K. and L.P.S. were supported by NIH P01 CA91955. C.C.M. was supported by NIH grants P01 CA91955, U54 CA217376, U2C CA233254, R01 CA140657 and CDMRP Breast Cancer Research Program Award BC132057. Marcin Imielinski was supported by Burroughs Wellcome Fund Career Award for Medical Scientists, Doris Duke Clinical Foundation Clinical Scientist Career Development Award, Starr Career Consortium Award, Melanoma Research Alliance Team Science Award, and NIH U24-CA15020. Kevin Hadi was supported by NIH/NCI F31 CA232465 Graduate Research Fellowship. Funding Information: This study was made possible by the lifelong commitment of Dr. Brian Reid to improving the lives of patients with Barrett{\textquoteright}s esophagus. We thank all the research participants who have made this study possible. We thank and acknowledge the support of the following medical and research staff who provided clinical care of the Seattle Barrett{\textquoteright}s Esophagus Program patients over the course of three decades and thus made this study possible: Dr. Douglas Levine, Dr. Peter Rabinovitch, Dr. Thomas Vaughan, Dr. Patricia Blount, Dr. Kamran Ayub, Dr. Shayan Irani, Dr. Michael Saunders, Dr. Rodger Haggitt, Dr. Robert Odze, Susan Irvine RN, Christine Karlsen, and Patricia Christopherson. David Cowan and Terri Watson provided database support. Tami Tolpa (Fig. ), Pritha Chanana, Timothy Chu, and Michael Northup helped with figure preparation. Jon Yamato and Diego Mallo provided additional analytical support. Amber Karnofski provided administrative support. T.G.P, P.C.G., K.M.O, C.A.S., B.J.R., and X.L. were supported by NIH P01 CA91955 and P30 CA015704. M.K.K. and L.P.S. were supported by NIH P01 CA91955. C.C.M. was supported by NIH grants P01 CA91955, U54 CA217376, U2C CA233254, R01 CA140657 and CDMRP Breast Cancer Research Program Award BC132057. Marcin Imielinski was supported by Burroughs Wellcome Fund Career Award for Medical Scientists, Doris Duke Clinical Foundation Clinical Scientist Career Development Award, Starr Career Consortium Award, Melanoma Research Alliance Team Science Award, and NIH U24-CA15020. Kevin Hadi was supported by NIH/NCI F31 CA232465 Graduate Research Fellowship. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-29767-7",
language = "English (US)",
volume = "13",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}