Endoscopic Samples Show Precancerous Genomic Changes in Barrett's Esophagus

The investigators analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples tissue taken from esophageal biopsies or endoscopic mucosal resections.

DNA was extracted and quantitated by fluorometry with the Invitrogen Qubit fluorometer and the Invitrogen Quant-iT double-strand DNA BR Assay Kit (Life Technologies; Grand Island, NY, USA). Samples from some patients were sequenced in either Life Technologies Ion Torrent and/or MiSeq (Illumina, San Diego, CA, USA) platforms, or in parallel.

The team found that found that progressors had mutations in 75% (6/8) of cases compared to 0% in non-progressors. The tumor suppressor protein p53 (TP53) was the most commonly mutated gene in the BE progressor group. Mutations were also found in the adenomatous polyposis coli (APC) and cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor genes. Next-generation sequencing from routine FFPE non-neoplastic Barrett’s esophagus samples can detect multiple mutations in minute areas of Barrett’s intestinal metaplasia (BIM) with high analytical sensitivity.

The authors concluded that that DNA from routine endoscopic FFPE samples of non-dysplastic BIM can be efficiently used to simultaneously detect multiple mutations by NGS with high analytical sensitivity, enabling the application of genomic testing of BE patients for improved HGD and EAC surveillance in clinical practice. Antonia R. Sepulveda, MD, PhD, Professor of Pathology and Cell Biology, and senior author of the study said, “The ability to detect mutations in non-neoplastic mucosa, quantitatively and with high detection sensitivity, makes it possible to use NGS mutational testing in the early detection and surveillance of patients who develop BE.” The study was published in the July 2015 issue of the Journal of Molecular Diagnostics.

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