Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus

Helen R. Moinova; Thomas LaFramboise; James D. Lutterbaugh; Apoorva Krishna Chandar; John Dumot; Ashley Faulx; Wendy Brock; Omar De la Cruz Cabrera; Kishore Guda; Jill S. Barnholtz-Sloan; Prasad G. Iyer; Marcia I. Canto; Jean S. Wang; Nicholas J. Shaheen; Prashanti N. Thota; Joseph E. Willis; Amitabh Chak; Sanford D. Markowitz

doi:10.1126/scitranslmed.aao5848

Research ArticleCancer

Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus

Helen R. Moinova¹,
Thomas LaFramboise²,³,
James D. Lutterbaugh¹,
Apoorva Krishna Chandar¹,
John Dumot¹,
Ashley Faulx¹,
Wendy Brock¹,
Omar De la Cruz Cabrera⁴,
Kishore Guda²,
Jill S. Barnholtz-Sloan²,
Prasad G. Iyer⁵,
Marcia I. Canto⁶,
Jean S. Wang⁷,
Nicholas J. Shaheen⁸,
Prashanti N. Thota⁹,
Joseph E. Willis²,¹⁰,¹¹,*,†,
Amitabh Chak¹,²,¹¹,*,† and
Sanford D. Markowitz¹,²,³,¹¹,*,†

¹Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
²Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
³Department of Genetics and Genome Sciences, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
⁴Department of Mathematical Sciences, Kent State University, Kent, OH 44242, USA.
⁵Barrett’s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
⁶Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
⁷Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁸Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁹Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
¹⁰Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
¹¹University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

↵*Corresponding author. Email: sxm10{at}cwru.edu (S.D.M.); josephe.willis{at}uhhospitals.org (J.E.W.); amitabh.chak{at}uhhospitals.org (A.C.)

↵† These authors contributed equally to this work.

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Science Translational Medicine 17 Jan 2018:
Vol. 10, Issue 424, eaao5848
DOI: 10.1126/scitranslmed.aao5848

Helen R. Moinova

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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Thomas LaFramboise

Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.Department of Genetics and Genome Sciences, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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James D. Lutterbaugh

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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Apoorva Krishna Chandar

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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John Dumot

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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Ashley Faulx

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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Wendy Brock

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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Omar De la Cruz Cabrera

Department of Mathematical Sciences, Kent State University, Kent, OH 44242, USA.

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Kishore Guda

Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

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Jill S. Barnholtz-Sloan

Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

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Prasad G. Iyer

Barrett’s Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.

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Marcia I. Canto

Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.

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Jean S. Wang

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

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Nicholas J. Shaheen

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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Prashanti N. Thota

Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

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Joseph E. Willis

Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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For correspondence: sxm10@cwru.edu josephe.willis@uhhospitals.org amitabh.chak@uhhospitals.org

Amitabh Chak

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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For correspondence: sxm10@cwru.edu josephe.willis@uhhospitals.org amitabh.chak@uhhospitals.org

Sanford D. Markowitz

Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.Department of Genetics and Genome Sciences, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.

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For correspondence: sxm10@cwru.edu josephe.willis@uhhospitals.org amitabh.chak@uhhospitals.org

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A test that goes down easy

Barrett’s esophagus is a premalignant condition of the distal esophagus that increases the risk of esophageal cancer. Unfortunately, screening for Barrett’s esophagus currently requires endoscopy, an invasive and expensive procedure, and thus, it is not routinely performed. Moinova et al. have now demonstrated a simplified approach to screening by identifying a pair of DNA methylation markers that correlate with the presence of Barrett’s esophagus. The authors also invented a swallowable balloon-based device that can capture DNA samples for methylation analysis and found that it is well tolerated in patients and provides >90% sensitivity and specificity compared to endoscopy, suggesting its potential as a screening method.

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Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett’s esophagus

A test that goes down easy

Science Translational Medicine

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