Comparison of cancer-associated genetic abnormalities in columnar-lined esophagus tissues with and without goblet cells

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, Zhongren Zhou

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

OBJECTIVE:: To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. BACKGROUND:: Barrett'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. METHODS:: Ninety 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. RESULTS:: Frequent 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. CONCLUSIONS:: This 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.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalAnnals of surgery
Volume260
Issue number1
DOIs
StatePublished - Jul 2014

Keywords

  • Barrett's esophagus
  • DNA copy number alterations
  • esophageal metaplasia
  • mutation
  • surveillance

Fingerprint Dive into the research topics of 'Comparison of cancer-associated genetic abnormalities in columnar-lined esophagus tissues with and without goblet cells'. Together they form a unique fingerprint.

Cite this