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High-Resolution Genomic Testing for Dysplasia and Adenocarcinoma Risk Stratification

Principal Investigator: Antonia Sepulveda

Institution: Columbia University

Year Awarded: 2014

Project Title: High-Resolution Genomic Testing for Dysplasia and Adenocarcinoma Risk Stratification of Barrett’s Esophagus Patients

Barrett’s esophagus (BE) is identified by the presence of intestinal metaplasia (BIM) in the esophagus, already harbors genomic alterations that characterize a field defect in the BE mucosa, and may progress to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and adenocarcinoma (EAC). Therefore, genomic mutations detectable in BE may serve as biomarkers to improve detection of dysplasia and EAC through risk stratification of patients for surveillance.

The hypothesis is that testing random pre-neoplastic BIM for gene copy number variations (CNV) and selected targeted genomic mutations using routine clinical endoscopic samples can predict the risk of development of dysplasia/esophageal adenocarcinoma with high sensitivity and specificity.

For CNV we will use the high-resolution OncoScan SNP-array platform validated in our pilot samples of BE endoscopic samples. Next Generation Sequencing (NGS) mutational testing will be done under separate funding.

Specific aim: To define the CNV and genomic mutations with highest sensitivity and specificity to predict progression of BIM to HGD/EAC by testing random BIM mucosa. We will study 90 tissue samples, from 30 BE patients who progressed to HGD/EAC and from 60 who did not progress, from a cohort of patients at Columbia University. Algorithms for identification of patients with high likelihood of progression to HGD/EAC will be established from the mutational patterns in the 2 patient groups. Availability of a sensitive and specific combinatorial genomic biomarker panel would be expected to be a major paradigm shift in the approach to BE surveillance, contributing to improve stratification of patients for surveillance and therapy.