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Published in: Surgical Endoscopy 7/2021

01-07-2021 | Barrett Esophagus | 2020 SAGES Oral

Somatic DNA copy number alterations in non-dysplastic Barrett’s esophagus

Authors: Zachary M. Callahan, Wennuan Liu, Jun Hou, S. Lilly Zheng, Jamaal Rehman, H. Mason Hedberg, Craig S. Brown, Bailey Su, Mikhail Attaar, Kristine Kuchta, MaryAnn Regner, JoAnn Carbray, Jianfeng Xu, Michael Ujiki

Published in: Surgical Endoscopy | Issue 7/2021

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Abstract

Background

The purpose of this study was to analyze non-dysplastic Barrett’s esophagus (NDBE) biopsy tissue and compare the rate of somatic DNA copy number alterations (CNAs) in patients who subsequently progressed to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) to those patients who did not.

Methods

A retrospectively collected database of Barrett’s esophagus (BE) patients spanning a 16-year period was queried. Patients who progressed from NDBE to HGD or EAC were identified and compared to patients who did not. Initial biopsy specimens were microdissected and extracted DNA underwent Multiplex Ligation-dependent Probe Amplification (MLPA) for CNAs. Comparisons between progressors and non-progressors were made with Fisher’s exact and two-sample t tests. Logistic regression assessed factors associated with progression.

Results

Of the 2459 patients in the BE database, 36 patients progressed from NDBE to either HGD or EAC. There were eight progressors who had biopsy specimens with adequate DNA for analysis. The progressor and non-progressor cohort had similar demographic information and medical history. The progressor group trended towards being older at diagnosis (72 ± 10 vs. 64 ± 13 years, p = 0.097) and fewer progressors reported reflux symptoms (50 vs. 94.7%, p < 0.001). Progressor specimens had more overall CNAs (75% vs. 33.6%, p = 0.026). On univariable analysis, there was an association between progression and absence of GERD symptoms (OR 16.54 [3.42–80.03], p = 0.001), any CNA (OR 5.10 [1.18–23.30], p = 0.035), and CNA in GATA6 or ERBB2 (OR 6.72 [1.18–38.22], p = 0.032).

Conclusions

Patients who progressed from NDBE to HGD or EAC were older at first diagnosis of BE and fewer of the progressors reported symptoms of reflux when compared to non-progressors. Progression was associated with the presence of any CNA and specific CNAs in GATA6 or ERBB2.
Literature
2.
go back to reference Anaparthy R, Gaddam S, Kanakadandi V, Alsop BR, Gupta N, Higbee AD, Wani SB, Singh M, Rastogi A, Bansal A, Cash BD, Young PE, Lieberman DA, Falk GW, Vargo JJ, Thota P, Sampliner RE, Sharma P (2013) Association between length of Barrett’s esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia. Clin Gastroenterol Hepatol 11:1430–1436. https://doi.org/10.1016/j.cgh.2013.05.007CrossRefPubMed Anaparthy R, Gaddam S, Kanakadandi V, Alsop BR, Gupta N, Higbee AD, Wani SB, Singh M, Rastogi A, Bansal A, Cash BD, Young PE, Lieberman DA, Falk GW, Vargo JJ, Thota P, Sampliner RE, Sharma P (2013) Association between length of Barrett’s esophagus and risk of high-grade dysplasia or adenocarcinoma in patients without dysplasia. Clin Gastroenterol Hepatol 11:1430–1436. https://​doi.​org/​10.​1016/​j.​cgh.​2013.​05.​007CrossRefPubMed
3.
go back to reference Wani S, Falk G, Hall M, Gaddam S, Wang A, Gupta N, Singh M, Singh V, Chuang K-Y, Boolchand V, Gavini H, Kuczynski J, Sud P, Reddymasu S, Bansal A, Rastogi A, Mathur SC, Young P, Cash B, Lieberman DA, Sampliner RE, Sharma P (2011) Patients with nondysplastic Barrett’s esophagus have low risks for developing dysplasia or esophageal adenocarcinoma. Clin Gastroenterol Hepatol 9:220–227. https://doi.org/10.1016/j.cgh.2010.11.008 (quiz e26)CrossRefPubMed Wani S, Falk G, Hall M, Gaddam S, Wang A, Gupta N, Singh M, Singh V, Chuang K-Y, Boolchand V, Gavini H, Kuczynski J, Sud P, Reddymasu S, Bansal A, Rastogi A, Mathur SC, Young P, Cash B, Lieberman DA, Sampliner RE, Sharma P (2011) Patients with nondysplastic Barrett’s esophagus have low risks for developing dysplasia or esophageal adenocarcinoma. Clin Gastroenterol Hepatol 9:220–227. https://​doi.​org/​10.​1016/​j.​cgh.​2010.​11.​008 (quiz e26)CrossRefPubMed
4.
go back to reference Duits LC, van der Wel MJ, Cotton CC, Phoa KN, Ten Kate FJW, Seldenrijk CA, Offerhaus GJA, Visser M, Meijer SL, Mallant-Hent RC, Krishnadath KK, Pouw RE, Tijssen JGP, Shaheen NJ, Bergman JJGHM (2017) Patients with Barrett’s esophagus and confirmed persistent low-grade dysplasia are at increased risk for progression to neoplasia. Gastroenterology 152:993–1001.e1. https://doi.org/10.1053/j.gastro.2016.12.008CrossRefPubMed Duits LC, van der Wel MJ, Cotton CC, Phoa KN, Ten Kate FJW, Seldenrijk CA, Offerhaus GJA, Visser M, Meijer SL, Mallant-Hent RC, Krishnadath KK, Pouw RE, Tijssen JGP, Shaheen NJ, Bergman JJGHM (2017) Patients with Barrett’s esophagus and confirmed persistent low-grade dysplasia are at increased risk for progression to neoplasia. Gastroenterology 152:993–1001.e1. https://​doi.​org/​10.​1053/​j.​gastro.​2016.​12.​008CrossRefPubMed
7.
go back to reference Bird-Lieberman EL, Dunn JM, Coleman HG, Lao-Sirieix P, Oukrif D, Moore CE, Varghese S, Johnston BT, Arthur K, McManus DT, Novelli MR, O’Donovan M, Cardwell CR, Lovat LB, Murray LJ, Fitzgerald RC (2012) Population-based study reveals new risk-stratification biomarker panel for Barrett’s esophagus. Gastroenterology 143:927–35.e3. https://doi.org/10.1053/j.gastro.2012.06.041CrossRefPubMed Bird-Lieberman EL, Dunn JM, Coleman HG, Lao-Sirieix P, Oukrif D, Moore CE, Varghese S, Johnston BT, Arthur K, McManus DT, Novelli MR, O’Donovan M, Cardwell CR, Lovat LB, Murray LJ, Fitzgerald RC (2012) Population-based study reveals new risk-stratification biomarker panel for Barrett’s esophagus. Gastroenterology 143:927–35.e3. https://​doi.​org/​10.​1053/​j.​gastro.​2012.​06.​041CrossRefPubMed
8.
go back to reference Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, Shim B, Ramos AH, Saksena G, Baca SC, Baselga J, Tabernero J, Barretina J, Enzinger PC, Corso G, Roviello F, Lin L, Bandla S, Luketich JD, Pennathur A, Meyerson M, Ogino S, Shivdasani RA, Beer DG, Godfrey TE, Beroukhim R, Bass AJ (2012) Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 72:4383–4393. https://doi.org/10.1158/0008-5472.CAN-11-3893CrossRefPubMedPubMedCentral Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, Shim B, Ramos AH, Saksena G, Baca SC, Baselga J, Tabernero J, Barretina J, Enzinger PC, Corso G, Roviello F, Lin L, Bandla S, Luketich JD, Pennathur A, Meyerson M, Ogino S, Shivdasani RA, Beer DG, Godfrey TE, Beroukhim R, Bass AJ (2012) Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res 72:4383–4393. https://​doi.​org/​10.​1158/​0008-5472.​CAN-11-3893CrossRefPubMedPubMedCentral
9.
go back to reference Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho Y-J, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao M-S, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463:899–905. https://doi.org/10.1038/nature08822CrossRefPubMedPubMedCentral Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho Y-J, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao M-S, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463:899–905. https://​doi.​org/​10.​1038/​nature08822CrossRefPubMedPubMedCentral
10.
go back to reference Weaver JMJ, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong C-AJ, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O’Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, Edwards PAW, Rosenfeld N, Tavaré S, Fitzgerald RC, OCCAMS consortium (2014) Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet 46:837–843. https://doi.org/10.1038/ng.3013CrossRefPubMedPubMedCentral Weaver JMJ, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong C-AJ, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O’Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, Edwards PAW, Rosenfeld N, Tavaré S, Fitzgerald RC, OCCAMS consortium (2014) Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet 46:837–843. https://​doi.​org/​10.​1038/​ng.​3013CrossRefPubMedPubMedCentral
13.
go back to reference Li X, Galipeau PC, Paulson TG, Sanchez CA, Arnaudo J, Liu K, Sather CL, Kostadinov RL, Odze RD, Kuhner MK, Maley CC, Self SG, Vaughan TL, Blount PL, Reid BJ (2014) Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett’s esophagus. Cancer Prev Res 7:114–127. https://doi.org/10.1158/1940-6207.CAPR-13-0289CrossRef Li X, Galipeau PC, Paulson TG, Sanchez CA, Arnaudo J, Liu K, Sather CL, Kostadinov RL, Odze RD, Kuhner MK, Maley CC, Self SG, Vaughan TL, Blount PL, Reid BJ (2014) Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett’s esophagus. Cancer Prev Res 7:114–127. https://​doi.​org/​10.​1158/​1940-6207.​CAPR-13-0289CrossRef
17.
go back to reference Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu M-C, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay M-A, Riva A, Crown J, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283. https://doi.org/10.1056/NEJMoa0910383CrossRefPubMedPubMedCentral Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu M-C, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay M-A, Riva A, Crown J, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283. https://​doi.​org/​10.​1056/​NEJMoa0910383CrossRefPubMedPubMedCentral
Metadata
Title
Somatic DNA copy number alterations in non-dysplastic Barrett’s esophagus
Authors
Zachary M. Callahan
Wennuan Liu
Jun Hou
S. Lilly Zheng
Jamaal Rehman
H. Mason Hedberg
Craig S. Brown
Bailey Su
Mikhail Attaar
Kristine Kuchta
MaryAnn Regner
JoAnn Carbray
Jianfeng Xu
Michael Ujiki
Publication date
01-07-2021
Publisher
Springer US
Published in
Surgical Endoscopy / Issue 7/2021
Print ISSN: 0930-2794
Electronic ISSN: 1432-2218
DOI
https://doi.org/10.1007/s00464-020-07859-z

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