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.
The Wistar Institute, 3601 Spruce St., Philadelphia, Pennsylvania 19104, USA. cmaley@alum.mit.edu
Carlo C
CC
Maley
Patricia C
PC
Galipeau
Jennifer C
JC
Finley
V Jon
VJ
Wongsurawat
Xiaohong
X
Li
Carissa A
CA
Sanchez
Thomas G
TG
Paulson
Patricia L
PL
Blount
Rosa-Ana
RA
Risques
Peter S
PS
Rabinovitch
Brian J
BJ
Reid
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