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Brian J. Reid, MD, PhD and Patricia C. Galipeau, Fred Hutchinson Cancer Research Center

January 24, 2017

Brian J. Reid, MD, PhD
Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Center, Professor of Medicine, Genome Sciences Adjunct Professor, University of Washington School of Medicine

Patricia C. Galipeau
Genomics Research Manager, Reid Laboratory, Fred Hutchinson Cancer Research Center

Q: What is the focus of your research?

A: Our research, supported by a grant from the National Institutes of Health and National Cancer Institute, is focused on somatic genetic changes – a genetic alteration acquired by a cell that can be passed to the progeny of the mutated cell in the course of cell division – in Barrett’s esophagus. This is a condition in which the lining of the esophagus changes to a new type of lining that resembles the lining of the small intestine and has many features, such as the ability to secrete a mucus layer, that help protect against reflux of injurious and mutagenic stomach contents such as acid and bile in the area where the esophagus is joined to the stomach.

Barrett’s esophagus is the only known predecessor to esophageal adenocarcinoma, an extremely aggressive cancer with a high-morbidity and mortality rate, which has increased in frequency in the U.S. and Western regions, such as Western Europe and Australia. This highly genetically complex cancer is very difficult to treat. It has an extremely high mutation rate, with the highest rate of whole genome doubling among all cancers, very frequently leading to resistance to therapy.

Barrett’s esophagus, a challenging disease to manage clinically, is characterized by common challenges of early cancer detection. It’s difficult to determine which patients to screen and when to screen them. Currently, 95 percent of patients with Barrett’s esophagus are never going to progress to esophageal adenocarcinoma. Doctors too often over diagnose, bringing many of these patients into the medical system for unnecessary and costly interventions including endoscopies, biopsies and ablations. As a result, patients become “worried well” – living with the constant fear of developing cancer, and leaving them in a cycle of elation when the doctors do not detect cancer or a high risk of cancer at endoscopy and despair as they return for follow-up endoscopies typically leading to more elation when the follow-up endoscopies are negative.

The foundation of our research is to be able to distinguish which patients with Barrett’s esophagus will develop esophageal adenocarcinoma and which patients will not. We are hoping that our findings will not only prevent over diagnosis, but also address under diagnosis – where current screening and surveillance fails to identify people with esophageal adenocarcinoma until they are present with an advanced cancer. The goal of our research is to identify, through whole genome sequencing and analysis, which Barrett’s esophagus patients are among the 5 percent who will progress to cancer.


Q: What collaborative research are you working on with NYGC?

A: Together with NYGC project managers, researchers and the bioinformatics team, we are collaborating on a case-control study. It involves whole genome sequencing to compare the variations in somatic genomes over space in the esophagus and over follow-up time in individuals with Barrett’s esophagus who progressed to esophageal adenocarcinoma, to the variations found in non-progressors who remained cancer-free.

Initially we completed a pilot study with NYGC that that involved a small number of esophageal samples that had been mapped spatially and collected over time. Based on the successful collaboration throughout the pilot study, we are now continuing our work with the Center on a larger project involving more than 420 samples, which include samples that have been collected over the past two decades.


Q: Why did you choose to collaborate with NYGC?

A: In preparation for our larger whole genome sequencing study, we sought to identify a high-quality sequencing service provider, who also had a skilled bioinformatics team with the flexibility to collaborate and meet the unique needs of our study while staying within budget.

This led us to invite NYGC representatives to the Fred Hutchinson Cancer Center in Seattle to further explore the potential for collaboration. Our interactions were all very positive and after meeting the team face-to-face, we felt confident in engaging in this collaboration.


Q: How was your experience working with NYGC?

A: We’ve had a tremendously positive experience collaborating with NYGC. The sample quality control process conducted by the Center was rigorous and the coverage and quality of the sequencing met a very high standard. The project managers we have worked with at NYGC have been cordial, organized, and highly responsive. Communication about questions, data transfers, meetings, budgets, and timelines have been addressed promptly and thoroughly.

One of the things that really impressed us was NYGC’s ability to run their standard analytic pipeline, yet remain nimble and flexible enough to adapt to our requests for additional bioinformatics tools to meet the very specific needs of our study.


Q: In what ways did collaborating with NYGC benefit your research?

A: We will gain a more complete view of the unique genetic mutation signatures of this cancer precursor using whole genome sequencing. With the increasing technical and informatics tools to comprehensively measure the genome, we are now able to study all aspects of how the genome is evolving over space and time before the development of cancer.

Collaborating with NYGC allowed us to conduct a critical pilot study in preparation for a large whole genome sequencing project, which is now ongoing. By working with NYGC researchers at this early stage, we were able customize the analytical pipeline and organize our personal and compute resources at our own institution in advance of the larger project. We’ve found NYGC to be much more than just a service provider; they demonstrated the ability to consistently implement standardized analytical pipelines and the flexibility to explore additional analyses to address the unique questions of our study. There has been excellent collaboration throughout the entire process, and we look forward to jointly publishing our findings with NYGC when the study is completed.

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