Program Official

Principal Investigator

Tony E
Awardee Organization

Boston University Medical Campus
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Development of diagnostic and prognostic tests for esophageal adenocarcinoma

The primary goal of this proposal is to develop novel molecular approaches for early detection of esophageal adenocarcinoma (EAC). EAC arises in the setting of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE); a metaplastic change resulting from GERD. This knowledge has driven endoscopic screening and surveillance recommendations for individuals with GERD and BE but compliance is low and the vast majority of new EAC cases are still diagnosed at late stage, when the tumor is inoperable and prognosis is extremely poor. Over the past 6-8 years, we have developed a highly collaborative, multi-institutional and multidisciplinary team focused on the development of clinically useful biomarkers for EAC. This proposal will build on our previously funded projects and the clinical and technical resources available to us through these studies, in order to evaluate two different approaches to early detection of EAC. The first approach is based on detection of somatic mutation and DNA copy number abnormality signatures in esophageal cytology samples. Published studies and our own ongoing work strongly indicate that accumulation of somatic mutations and major chromosomal rearrangements drive the progression from BE to EAC. We believe that these changes can be leveraged to identify a genomic signature for progression that can be detected in cytology samples using a targeted next-generation sequencing (NGS) test. Identification of the genomic signature is ongoing in our group through large-scale comparative sequencing of EAC and pre-neoplastic tissue samples. To evaluate the effectiveness of this signature in identifying progression, we are currently collecting ~350 esophageal cytology samples using an encapsulated sponge called the EsophaCap™. This device is not yet commercially available, but has been provided to us under arrangement with CapNostics LLC and is currently approved for investigational testing in the USA and Canada. These unique data and tissue resources will be used in Specific Aim 1 to evaluate the sensitivity and specificity of a targeted NGS analysis of esophageal cytology samples to detect dysplasia and early EAC. The second approach also leverages our large-scale sequencing data and targeted sequencing assays, but in this case we will evaluate the detection of mutations in circulating, cell-free DNA isolated from plasma as a biomarker for EAC. We are currently collecting plasma from all patients who swallow the EsophaCap™ device and this provides an excellent tissue resource in which to test detection of circulating tumor DNA (ctDNA). To aid in the detection of ctDNA, we have developed an ultra-sensitive NGSbased assay that can detect mutations at multiple loci with sensitivity as low as 0.05% (1/2000) mutant allele fraction. These resources will be used in Specific Aim 2 in order to evaluate the sensitivity and specificity of ctDNA for detection of stage I and II EAC. Finally, studies indicate that ctDNA detection may have prognostic value. In Specific Aim 3 we will evaluate the prognostic value of ctDNA in stage I and II EAC patients with the hope that this may prove useful for directing neoadjuvant therapy in these patients.


  • Egyud M, Tejani M, Pennathur A, Luketich J, Sridhar P, Yamada E, Ståhlberg A, Filges S, Krzyzanowski P, Jackson J, Kalatskaya I, Jiao W, Nielsen G, Zhou Z, Litle V, Stein L, Godfrey T. Detection of Circulating Tumor DNA in Plasma: A Potential Biomarker for Esophageal Adenocarcinoma. The Annals of thoracic surgery. 2019 Aug;108(2):343-349. Epub 2019 May 3. PMID: 31059681
  • Egyud M, Sridhar P, Devaiah A, Yamada E, Saunders S, Ståhlberg A, Filges S, Krzyzanowski PM, Kalatskaya I, Jiao W, Stein LD, Jalisi S, Godfrey TE. Plasma circulating tumor DNA as a potential tool for disease monitoring in head and neck cancer. Head & neck. 2019 May;41(5):1351-1358. Epub 2018 Dec 15. PMID: 30554450
  • Zhou Z, Kalatskaya I, Russell D, Marcon N, Cirocco M, Krzyzanowski PM, Streutker C, Liang H, Litle VR, Godfrey TE, Stein L. Combined EsophaCap cytology and MUC2 immunohistochemistry for screening of intestinal metaplasia, dysplasia and carcinoma. Clinical and experimental gastroenterology. 2019 May 15;12:219-229. doi: 10.2147/CEG.S186958. eCollection 2019. PMID: 31190949
  • Johansson G, Andersson D, Filges S, Li J, Muth A, Godfrey TE, Ståhlberg A. Considerations and quality controls when analyzing cell-free tumor DNA. Biomolecular detection and quantification. 2019 Feb 13;17:100078. doi: 10.1016/j.bdq.2018.12.003. eCollection 2019 Mar. PMID: 30906693
  • Filges S, Yamada E, Ståhlberg A, Godfrey TE. Impact of Polymerase Fidelity on Background Error Rates in Next-Generation Sequencing with Unique Molecular Identifiers/Barcodes. Scientific reports. 2019 Mar 5;9(1):3503. PMID: 30837525
  • He HJ, Stein EV, Konigshofer Y, Forbes T, Tomson FL, Garlick R, Yamada E, Godfrey T, Abe T, Tamura K, Borges M, Goggins M, Elmore S, Gulley ML, Larson JL, Ringel L, Haynes BC, Karlovich C, Williams PM, Garnett A, Ståhlberg A, Filges S, Sorbara L, Young MR, Srivastava S, Cole KD. Multilaboratory Assessment of a New Reference Material for Quality Assurance of Cell-Free Tumor DNA Measurements. The Journal of molecular diagnostics : JMD. 2019 Jul;21(4):658-676. Epub 2019 May 2. PMID: 31055023

Clinical Trials

Study Name Clinical Trial ID
Esophageal Cancer Risk Registry NCT00260585