• Santhoshi Bandla, Jeffrey H Peters, David Ruff, Shiaw-Min Chen, Chieh-Yuan Li, Kunchang Song, Kimberly Thoms, Virginia R Litle, Thomas Watson, Nikita Chapurin, Michal Lada, Arjun Pennathur, James D Luketich, Derick Peterson, Austin Dulak, Lin Lin, Adam Bass, David G Beer, Tony E Godfrey, and Zhongren Zhou.
• *Departments of Surgery ‡Pathology, and ‖Biostatistics, University of Rochester Medical Center, Strong Memorial Hospital, Rochester, NY †Life Technologies, Foster City, CA **Dana Farber Cancer Center, Boston, MA ††University of Michigan, Ann Arbor, MI ¶University of Pittsburgh, Pittsburgh, PA; and §Department of Surgery, Boston University, Boston, MA.
• Ann. Surg. 2014 Jul 1; 260 (1): 72-80.

ObjectiveTo determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells.BackgroundBarrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC.MethodsNinety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing.ResultsFrequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples.ConclusionsThis study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.

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