Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus

abstract: Surveillance of Barrett’s oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm[superscript 2] (95% CI: 0.09–4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett’s and that the malignant potential of ‘benign’ Barrett’s lesions is predetermined, with important implications for surveillance programs.The final version of this article, as published in Nature Communications, can be viewed online at: https://www.nature.com/articles/ncomms1215

A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus

National Cancer Institute grants U01 CA152926 (CISNET) (to EGL, JJ, and WDH) and U01 CA182940 (BG-U01) (to EGL and WDH). National Science Foundation (www.nsf.gov) under grant no. DGE-0718124 (to KC

Classifying the evolutionary and ecological features of neoplasms

The consensus conference was supported by Wellcome Genome Campus Advanced Courses and Scientific Conferences. C.C.M. is supported in part by US NIH grants P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657 as well as CDMRP Breast Cancer Research Program Award BC132057. M.J. is supported by NIH grant K99CA201606. K.S.A. is supported by NCI 5R21 CA196460. K. Polyak is supported by R35 CA197623, U01 CA195469, U54 CA193461, and the Breast Cancer Research Foundation. K.J.P. is supported by NIH grants CA143803, CA163124, CA093900 and CA143055. D.P. is supported by the European Research Council (ERC-617457- PHYLOCANCER), the Spanish Ministry of Economy and Competitiveness (BFU2015-63774-P) and the Education, Culture and University Development Department of the Galician Government. K.S.A. is supported in part by the Breast Cancer Research Foundation and NCI R21CA196460. C.S. is supported by the Royal Society, Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169), NovoNordisk Foundation (ID 16584), the Breast Cancer Research Foundation (BCRF), the European Research Council (THESEUS) and Marie Curie Network PloidyNet. T.A.G. is a Cancer Research UK fellow and a Wellcome Trust funded Investigator. E.S.H. is supported by R01 CA185138-01 and W81XWH-14-1-0473. M.Gerlinger is supported by Cancer Research UK and The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. M.Ge., M.Gr., Y.Y., and A.So. were also supported in part by the Wellcome Trust [105104/Z/14/Z]. J.D.S. holds the Edward B. Clark, MD Chair in Pediatric Research, and is supported by the Primary Children's Hospital (PCH) Pediatric Cancer Research Program, funded by the Intermountain Healthcare Foundation and the PCH Foundation. A.S. is supported by the Chris Rokos Fellowship in Evolution and Cancer. Y.Y. is a Cancer Research UK fellow and supported by The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. E.S.H. was supported in part by PCORI grants 1505–30497 and 1503–29572, NIH grants R01 CA185138, T32 CA093245, and U10 CA180857, CDMRP Breast Cancer Research Program Award BC132057, a CRUK Grand Challenge grant, and the Breast Cancer Research Foundation. A.R.A.A. was funded in part by NIH grant U01CA151924. A.R.A.A., R.G. and J.S.B. were funded in part by NIH grant U54CA193489

Evolution of Barrett's esophagus through space and time at single-crypt and whole-biopsy levels

This work was primarily supported by National Cancer Institute grants R01 CA140657 and P01 CA091955 (T.G.P., X.L., C.A.S., B.J.R., M.K.K., and C.C.M.). This work was also supported in part by NIH grants R01 CA149566, R01 CA170595, and R01 CA185138, as well as CDMRP Breast Cancer Research Program Award BC132057. T.A. G. was supported by Cancer Research UK (A19771).

A Big Bang model of human colorectal tumor growth

The project described was supported in part by an award to C.C. from the V Foundation for Cancer Research and by award numbers P30CA014089, R21CA149990 and R21CA151139 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. M.F.P. was supported by a grant from the California Institute for Regenerative Medicine (CIRM).

Life History Trade-Offs in Tumors.

Purpose: In this paper, we provide an overview of a life history theory and how it applies to cancer evolution. Recent Findings: We review the literature on trade-offs in tumors, focusing on the trade-offs among cellular proliferation, survival, and motility. Trade-offs are critical natural constraints for almost all evolutionary processes. Many ecological studies show that trade-offs among these cellular functions maintain a genetic diversity. In addition, these trade-offs are not fixed, but rather can shift depending on the ecological circumstances in the microenvironment. This can lead to selection for the cellular capacity to respond to these differing microenvironments in ways that promote the fitness of the cancer cell. We relate these life history trade-offs to the recently developed Evo-Eco indexes and discuss how life history theory can help refine our measures of tumor evolution and ecology. Summary: Life history theory provides a framework for understanding how the spatial and temporal variability in the tumor microenvironment-in particular resources and threats-affect trade-offs among cell survival, cell proliferation, and cell migration. We discuss how these trade-offs can potentially be leveraged in cancer therapy to increase the effectiveness of treatment