A Comprehensive Survey of Clonal Diversity Measures in Barrett's Esophagus as Biomarkers of Progression to Esophageal Adenocarcinoma

被引:122
作者
Merlo, Lauren M. F. [1 ]
Shah, Najaf A. [2 ]
Li, Xiaohong [4 ]
Blount, Patricia L. [4 ,5 ,6 ]
Vaughan, Thomas L. [5 ,7 ]
Reid, Brian J. [4 ,5 ,6 ,8 ]
Maley, Carlo C. [1 ,2 ,3 ]
机构
[1] Wistar Inst Anat & Biol, Mol & Cellular Oncogenesis Program, Philadelphia, PA 19104 USA
[2] Univ Penn, Genom & Computat Biol Grad Grp, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA
[4] Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98104 USA
[5] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA
[6] Univ Washington, Dept Med, Seattle, WA USA
[7] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
[8] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
关键词
CANCER-RISK; ORAL-CANCER; DYSPLASIA; CARCINOGENESIS; EVOLUTIONARY; DISCOVERY; LESIONS; MODEL;
D O I
10.1158/1940-6207.CAPR-10-0108
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Cancer Prev Res; 3(11); 1388-97. (C) 2010 AACR.
引用
收藏
页码:1388 / 1397
页数:10
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