Genetic clonal diversity predicts progression to esophageal adenocarcinoma.
Neoplasms are thought to progress to cancer through genetic instability generating cellular diversity and clonal expansions driven by selection for mutations in cancer genes. Despite advances in the study of molecular biology of cancer genes, relatively little is known about evolutionary mechanisms that drive neoplastic progression. It is unknown, for example, which may be more predictive of future progression of a neoplasm: genetic homogenization of the neoplasm, possibly caused by a clonal expansion, or the accumulation of clonal diversity. Here, in a prospective study, we show that clonal diversity measures adapted from ecology and evolution can predict progression to adenocarcinoma in the premalignant condition known as Barrett's esophagus, even when controlling for established genetic risk factors, including lesions in TP53 (p53; ref. 6) and ploidy abnormalities. Progression to cancer through accumulation of clonal diversity, on which natural selection acts, may be a fundamental principle of neoplasia with important clinical implications.
Maley
Carlo C
CC
The Wistar Institute, 3601 Spruce St., Philadelphia, Pennsylvania 19104, USA. cmaley@alum.mit.edu
Galipeau
Patricia C
PC
Finley
Jennifer C
JC
Wongsurawat
V Jon
VJ
Li
Xiaohong
X
Sanchez
Carissa A
CA
Paulson
Thomas G
TG
Blount
Patricia L
PL
Risques
Rosa-Ana
RA
Rabinovitch
Peter S
PS
Reid
Brian J
BJ
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity