title: Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett's esophagus.
abstract: OBJECTIVE
  Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology. We, therefore, examined the presence and extent of genomic instability in advanced and less advanced BE histology using mutational load (ML).
  
  
  METHODS
  ML summarized the presence and clonality of loss of heterozygosity (LOH) mutations and the emergence of new alleles, manifested as microsatellite instability (MSI) mutations, in ten genomic loci around tumor suppressor genes associated with EAC. The ML of 877 microdissected targets from BE biopsies was correlated to their histology. Histological targets were categorized into three levels: no ML, low ML, and high ML.
  
  
  RESULTS
  Increasing ML correlated with increasingly severe histology. By contrast, proportions of targets that lacked mutations decreased with increasingly severe histology. A portion of targets with non-dysplastic and low-grade histology shared a similar ML as those with higher risk and EAC disease. The addition of MSI characterization to ML helped to differentiate the ML between advanced and less advanced histology.
  
  
  CONCLUSIONS
  Given that EAC is associated with accumulated genomic instability, high ML in less severe histology may identify BE disease at greater risk of progression to EAC. ML may help to better manage BE in early histological stages and when histology alone provides insufficient information.
authors.affiliation: Norwalk Hospital, Norwalk, CT, USA.
authors.forename: Harshit S
authors.initials: HS
authors.lastname: Khara
authors.forename: Sara A
authors.initials: SA
authors.lastname: Jackson
authors.forename: Saraswathi
authors.initials: S
authors.lastname: Nair
authors.forename: Georgios
authors.initials: G
authors.lastname: Deftereos
authors.forename: Shweta
authors.initials: S
authors.lastname: Patel
authors.forename: Jan F
authors.initials: JF
authors.lastname: Silverman
authors.forename: Eric
authors.initials: E
authors.lastname: Ellsworth
authors.forename: Cameron
authors.initials: C
authors.lastname: Sumner
authors.forename: Brendan
authors.initials: B
authors.lastname: Corcoran
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Smith
authors.forename: Sydney
authors.initials: S
authors.lastname: Finkelstein
authors.forename: Seth A
authors.initials: SA
authors.lastname: Gross
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D001706:Biopsy; D015331:Cohort Studies; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005500:Follow-Up Studies; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins