Optimization and validation of a biomarker panel for risk stratification in Barrett's esophagus

Intestinalization of the esophagus, termed Barrett’s esophagus (BE), is thought to develop in response to chronic acid and bile reflux and carries great clinical significance because it is the precursor to esophageal adenocarcinoma (EAC). The incidence of BE is quite high, estimated to be found in at least 1:100 people. While relatively few with BE progress to cancer there is great importance to being able to detect and treat those at risk of progression as EAC is an aggressive cancer with potential for early spread. Efforts to screen for high-risk disease in those with BE have, to date, not been very successful. Therefore, there is profound need to define the process by which BE progresses into EAC, to develop biomarkers to diagnose early progression and assess progression risk in BE tissues as well as to develop novel therapies for treatment. The objective of this diversity supplement proposal is to provide training to a promising URM researcher to prepare her for a PhD program while providing a significant contribution to the parent R37 project. Specifically, this proposal will perform enhanced methylation analysis utilizing a new sequencing based approach. Additionally, this proposal will explore how this additional sequencing data may be used to improve our somatic DNA copy number analysis. Combined, these studies will be a valuable component of our overall objective to develop a molecular risk stratification assay for patients with Barrett’s esophagus. In addition to the expert group of researchers that has been established as part of the parent R37 project, the candidate will be co-mentored with Dr. Franklin Huang. Dr. Huang is an expert cancer computational biologist who has a laboratory near Dr. Stachler. This will allow the candidate to receive strong mentorship and career development on the full spectrum of cancer genomics through the aims listed below. Aim 1: Identify and validate a set of methylation-based biomarkers that best risk stratify patients with a diagnosis of non-dysplastic Barrett’s esophagus or low-grade dysplasia. Aim 2: Adapt standard computational approaches of DNA copy number analysis to utilize sequencing data generated from sequencing based methylation analysis. A major goal of the supplement candidate is to expand her abilities in NGS based ‘omic’ analysis in both the traditional wet lab, computational, and integrated analysis of the data generated in preparation for applying to graduate school where she hopes to pursue further studies in cancer genomics. Therefore, the performing of methylation analysis and developing methods to determine copy number calling from the sequencing data will be an ideal platform for Lorena Benitez-Rivera to develop her expertise in cancer genomics.