Center for Evolution and Cancer
Center for Evolution and Cancer
Li X.,Fred Hutchinson Cancer Research Center |
Li X.,University of Washington |
Galipeau P.C.,Fred Hutchinson Cancer Research Center |
Paulson T.G.,Fred Hutchinson Cancer Research Center |
And 14 more authors.
Cancer Prevention Research | Year: 2014
All cancers are believed to arise by dynamic, stochastic somatic genomic evolution with genome instability, generation of diversity, and selection of genomic alterations that underlie multistage progression to cancer. Advanced esophageal adenocarcinomas have high levels of somatic copy number alterations. Barrett's esophagus is a risk factor for developing esophageal adenocarcinoma, and somatic chromosomal alterations (SCA) are known to occur in Barrett's esophagus. The vast majority (~95%) of individuals with Barrett's esophagus do not progress to esophageal adenocarcinoma during their lifetimes, but a small subset develop esophageal adenocarcinoma,many ofwhich arise rapidly even in carefullymonitored patients without visible endoscopic abnormalities at the index endoscopy. Using a well-designed, longitudinal case-cohort study, we characterized SCA as assessed by single-nucleotide polymorphism arrays over space and time in 79*progressors*with Barrett's esophagus as they approach the diagnosis of cancer and 169*nonprogressors*with Barrett's esophaguswho did not progress to esophageal adenocarcinomaover more than 20,425 personmonths of follow-up. The genomes of nonprogressors typically had small localized deletions involving fragile sites and 9p loss/copy neutral LOH that generate little genetic diversity and remained relatively stable over prolonged follow-up. As progressors approach the diagnosis of cancer, their genomes developed chromosome instability with initial gains and losses, genomic diversity, and selection of SCAs followed by catastrophic genome doublings. Our results support a model of differential disease dynamics in which nonprogressor genomes largely remain stable over prolonged periods, whereas progressor genomes evolve significantly increased SCA and diversity within four years of esophageal adenocarcinoma diagnosis, suggesting a window of opportunity for early detection. ©2013 American Association for Cancer Research.
Alcock J.,University of New Mexico |
Maley C.C.,Center for Evolution and Cancer |
Maley C.C.,University of California at San Francisco |
Maley C.C.,Institute for Advanced Study Berlin |
And 4 more authors.
BioEssays | Year: 2014
Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating. © 2014 The Authors.