A comprehensive survey of clonal diversity measures in Barrett's esophagus as biomarkers of progression to esophageal adenocarcinoma.

Publication Type:

Journal Article

Source:

Cancer prevention research (Philadelphia, Pa.), Volume 3, Issue 11, p.1388-97 (2010)

Keywords:

2010, ADENOCARCINOMA, Adult, Aged, Barrett Esophagus, Cell Separation, Center-Authored Paper, Clone Cells, Collaborative Data Services Core Facility, DISEASE PROGRESSION, DNA Methylation, Esophageal Neoplasms, Female, Genotype, Humans, loss of heterozygosity, Male, Microsatellite Repeats, Middle Aged, Mutation, Nutrition Assessment Core Facility, Proportional Hazards Models, Public Health Sciences Division, Shared Resources, Specimen Processing Core Facility, Tumor Markers, Biological

Abstract:

Neoplastic progression is an evolutionary process driven by the generation of clonal diversity and natural selection on that diversity within a neoplasm. We hypothesized that clonal diversity is associated with risk of progression to cancer. We obtained molecular data from a cohort of 239 participants with Barrett's esophagus, including microsatellite shifts and loss of heterozygosity, DNA content tetraploidy and aneuploidy, methylation, and sequence mutations. Using these data, we tested all major diversity measurement methods, including genetic divergence and entropy-based measures, to determine which measures are correlated with risk of progression to esophageal adenocarcinoma. We also tested whether the use of different sets of loci and alterations to define clones (e.g., selectively advantageous versus evolutionarily neutral) improved the predictive value of the diversity indices. All diversity measures were strong and highly significant predictors of progression (Cox proportional hazards model, P < 0.001). The type of alterations evaluated had little effect on the predictive value of most of the diversity measures. In summary, diversity measures are robust predictors of progression to cancer in this cohort.