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

Lauren M F Merlo, Najaf A. Shah, Xiaohong Li, Patricia L. Blount, Thomas L. Vaughan, Brian J. Reid, Carlo Maley

Research output: Contribution to journalArticle

102 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1388-1397
Number of pages10
JournalCancer Prevention Research
Volume3
Issue number11
DOIs
StatePublished - Nov 2010
Externally publishedYes

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Barrett Esophagus
Adenocarcinoma
Biomarkers
Neoplasms
Tetraploidy
Genetic Selection
Loss of Heterozygosity
Entropy
Aneuploidy
Proportional Hazards Models
Microsatellite Repeats
Methylation
Clone Cells
Mutation
DNA
Surveys and Questionnaires

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A comprehensive survey of clonal diversity measures in Barrett's esophagus as biomarkers of progression to esophageal adenocarcinoma. / Merlo, Lauren M F; Shah, Najaf A.; Li, Xiaohong; Blount, Patricia L.; Vaughan, Thomas L.; Reid, Brian J.; Maley, Carlo.

In: Cancer Prevention Research, Vol. 3, No. 11, 11.2010, p. 1388-1397.

Research output: Contribution to journalArticle

Merlo, Lauren M F ; Shah, Najaf A. ; Li, Xiaohong ; Blount, Patricia L. ; Vaughan, Thomas L. ; Reid, Brian J. ; Maley, Carlo. / A comprehensive survey of clonal diversity measures in Barrett's esophagus as biomarkers of progression to esophageal adenocarcinoma. In: Cancer Prevention Research. 2010 ; Vol. 3, No. 11. pp. 1388-1397.
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