Advertisement

Digestive Diseases and Sciences

, Volume 63, Issue 8, pp 2059–2069 | Cite as

Molecular Evolution of Metaplasia to Adenocarcinoma in the Esophagus

  • William M. Grady
  • Ming Yu
Review

Abstract

Esophageal adenocarcinoma (EAC) develops from Barrett’s esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Epigenetic abnormalities, primary alterations in DNA methylation, are also frequently seen in BE and EAC. Candidate gene and array-based approaches have demonstrated that numerous tumor suppressor genes exhibit aberrant promoter methylation, and some of these altered genes are associated with the neoplastic progression of BE. It has also been shown that the BE and EAC epigenomes are characterized by hypomethylation of intragenic and non-coding regions Recent studies have also provided new insight into the evolutionary forces underlying the molecular alterations seen in BE and EAC and into the molecular pathogenesis of EAC.

Keywords

Barrett’s esophagus Esophageal adenocarcinoma Cancer genomics LOH Aneuploidy Genomic instability DNA methylation 

Notes

Acknowledgments

Support for this work was provided by National Institutes of Health (NIH) National Cancer Institute (NCI) RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, and P01CA077852 (WMG) and the DeGregorio Family Foundation and Lattner Family Foundation (WMG).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Barrett MT, Galipeau PC, Sanchez CA, et al. Determination of the frequency of loss of heterozygosity in esophageal adenocarcinoma by cell sorting, whole genome amplification and microsatellite polymorphisms. Oncogene. 1996;12:1873–1878.PubMedGoogle Scholar
  2. 2.
    Reid BJ, Barrett MT, Galipeau PC, et al. Barrett’s esophagus: ordering the events that lead to cancer. Eur J Cancer Prev. 1996;5:57–65.CrossRefPubMedGoogle Scholar
  3. 3.
    Barrett MT, Sanchez CA, Prevo LJ, et al. Evolution of neoplastic cell lineages in Barrett oesophagus. Nat Genet. 1999;22:106–109.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Munz B, Smola H, Engelhardt F, et al. Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair. EMBO J. 1999;18:5205–5215.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Flejou JF. Barrett’s oesophagus: from metaplasia to dysplasia and cancer. Gut. 2005;54:i6–i12.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Reid BJ, Levine DS, Longton G, et al. Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol. 2000;95:1669–1676.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Maley CC, Galipeau PC, Finley JC, et al. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet. 2006;38:468–473.CrossRefPubMedGoogle Scholar
  8. 8.
    McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16:717–727.CrossRefPubMedGoogle Scholar
  9. 9.
    Maley CC, Galipeau PC, Li X, et al. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett’s esophagus. Cancer Res. 2004;64:3414–3427.CrossRefPubMedGoogle Scholar
  10. 10.
    Werther M, Saure C, Pahl R, et al. Molecular genetic analysis of surveillance biopsy samples from Barrett’s mucosa—significance of sampling. Pathol Res Pract. 2008;204:285–294.CrossRefPubMedGoogle Scholar
  11. 11.
    Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194:23–28.CrossRefPubMedGoogle Scholar
  12. 12.
    Merlo LM, Pepper JW, Reid BJ, et al. Cancer as an evolutionary and ecological process. Nat Rev Cancer. 2006;6:924–935.CrossRefPubMedGoogle Scholar
  13. 13.
    Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481:306–313.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Vogelstein B, Fearon E, Hamilton S, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–532.CrossRefPubMedGoogle Scholar
  15. 15.
    Sottoriva A, Kang H, Ma Z, et al. A Big Bang model of human colorectal tumor growth. Nat Genet. 2015;47:209–216.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Rabinovitch PS, Reid BJ, Haggitt RC, et al. Progression to cancer in Barrett’s esophagus is associated with genomic instability. Lab Invest. 1989;60:65–71.PubMedGoogle Scholar
  17. 17.
    Maher CA, Wilson RK. Chromothripsis and human disease: piecing together the shattering process. Cell. 2012;148:29–32.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Stephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144:27–40.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Siegmund KD, Marjoram P, Woo YJ, et al. Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancers. Proc Natl Acad Sci USA. 2009;106:4828–4833.CrossRefPubMedGoogle Scholar
  20. 20.
    Ling S, Hu Z, Yang Z, et al. Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution. Proc Natl Acad Sci USA. 2015;112:E6496–E6505.CrossRefPubMedGoogle Scholar
  21. 21.
    Williams MJ, Werner B, Barnes CP, et al. Identification of neutral tumor evolution across cancer types. Nat Genet. 2016;48:238–244.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Uchi R, Takahashi Y, Niida A, et al. Integrated multiregional analysis proposing a new model of colorectal cancer evolution. PLoS Genet. 2016;12:e1005778.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Jung KW, Talley NJ, Romero Y, et al. Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett’s esophagus: a population-based study. Am J Gastroenterol. 2011;106:1447–1455. (quiz 1456).CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Baca SC, Prandi D, Lawrence MS, et al. Punctuated evolution of prostate cancer genomes. Cell. 2013;153:666–677.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Navin N, Kendall J, Troge J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472:90–94.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Humphries A, Cereser B, Gay LJ, et al. Lineage tracing reveals multipotent stem cells maintain human adenomas and the pattern of clonal expansion in tumor evolution. Proc Natl Acad Sci USA. 2013;110:E2490–E2499.CrossRefPubMedGoogle Scholar
  27. 27.
    Notta F, Chan-Seng-Yue M, Lemire M, et al. A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns. Nature. 2016;538:378–382.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Cross W, Graham TA, Wright NA. New paradigms in clonal evolution: punctuated equilibrium in cancer. J Pathol. 2016;240:126–136.CrossRefPubMedGoogle Scholar
  29. 29.
    Stachler MD, Taylor-Weiner A, Peng S, et al. Paired exome analysis of Barrett’s esophagus and adenocarcinoma. Nat Genet. 2015;47:1047–1055.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ross-Innes CS, Becq J, Warren A, et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma. Nat Genet. 2015;47:1038–1046.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Gregson EM, Bornschein J, Fitzgerald RC. Genetic progression of Barrett’s oesophagus to oesophageal adenocarcinoma. Br J Cancer. 2016;115:403–410.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Nones K, Waddell N, Wayte N, et al. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun. 2014;5:5224.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Contino G, Vaughan TL, Whiteman D, et al. The evolving genomic landscape of Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2017;153:657–673 e1.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Jankowski JA, Wright NA, Meltzer SJ, et al. Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Pathol. 1999;154:965–973.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Weaver JM, Ross-Innes CS, Shannon N, et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet. 2014;46:837–843.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kaz AM, Wong CJ, Luo Y, et al. DNA methylation profiling in Barrett’s esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses. Epigenetics. 2011;6:1403–1412.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Xu E, Gu J, Hawk ET, et al. Genome-wide methylation analysis shows similar patterns in Barrett’s esophagus and esophageal adenocarcinoma. Carcinogenesis. 2013;34:2750–2756.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Casson AG, Mukhopadhyay T, Cleary KR, et al. p53 gene mutations in Barrett’s epithelium and esophageal cancer. Cancer Res. 1991;51:4495–4499.PubMedGoogle Scholar
  39. 39.
    Wu TT, Watanabe T, Heitmiller R, et al. Genetic alterations in Barrett esophagus and adenocarcinomas of the esophagus and esophagogastric junction region. Am J Pathol. 1998;153:287–294.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Galipeau PC, Prevo LJ, Sanchez CA, et al. Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett’s) tissue. J Natl Cancer Inst. 1999;91:2087–2095.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Dulak AM, Stojanov P, Peng S, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45:478–486.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Cancer Genome Atlas Research N, Analysis Working Group, Agency BCC, Asan U, et al. Integrated genomic characterization of oesophageal carcinoma. Nature. 2017;541:169–175.CrossRefGoogle Scholar
  43. 43.
    Agrawal N, Jiao Y, Bettegowda C, et al. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov. 2012;2:899–905.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Streppel MM, Lata S, DelaBastide M, et al. Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett’s esophagus. Oncogene. 2014;33:347–357.CrossRefPubMedGoogle Scholar
  45. 45.
    Li X, Paulson TG, Galipeau PC, et al. Assessment of esophageal adenocarcinoma risk using somatic chromosome alterations in longitudinal samples in Barrett’s esophagus. Cancer Prev Res (Phila). 2015;8:845–856.CrossRefGoogle Scholar
  46. 46.
    Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet. 2008;9:465–476.CrossRefPubMedGoogle Scholar
  47. 47.
    Feinberg AP. The epigenetics of cancer etiology. Semin Cancer Biol. 2004;14:427–432.CrossRefPubMedGoogle Scholar
  48. 48.
    Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31:27–36.CrossRefPubMedGoogle Scholar
  49. 49.
    Sawan C, Herceg Z. Histone modifications and cancer. Adv Genet. 2010;70:57–85.PubMedGoogle Scholar
  50. 50.
    Ballestar E, Esteller M. Epigenetic gene regulation in cancer. Adv Genet. 2008;61:247–267.PubMedGoogle Scholar
  51. 51.
    Ting AH, McGarvey KM, Baylin SB. The cancer epigenome–components and functional correlates. Genes Dev. 2006;20:3215–3231.CrossRefPubMedGoogle Scholar
  52. 52.
    van Engeland M, Derks S, Smits KM, et al. Colorectal cancer epigenetics: complex simplicity. J Clin Oncol. 2011;29:1382–1391.CrossRefPubMedGoogle Scholar
  53. 53.
    Krause L, Nones K, Loffler KA, et al. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma. Carcinogenesis. 2016;37:356–365.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Wong DJ, Paulson TG, Prevo LJ, et al. p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium. Cancer Res. 2001;61:8284–8289.PubMedGoogle Scholar
  55. 55.
    Bian YS, Osterheld MC, Fontolliet C, et al. p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett’s esophagus. Gastroenterology. 2002;122:1113–1121.CrossRefPubMedGoogle Scholar
  56. 56.
    Eads CA, Lord RV, Wickramasinghe K, et al. Epigenetic patterns in the progression of esophageal adenocarcinoma. Cancer Res. 2001;61:3410–3418.PubMedGoogle Scholar
  57. 57.
    Eads CA, Lord RV, Kurumboor SK, et al. Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Cancer Res. 2000;60:5021–5026.PubMedGoogle Scholar
  58. 58.
    Prevo LJ, Sanchez CA, Galipeau PC, et al. p53-mutant clones and field effects in Barrett’s esophagus. Cancer Res. 1999;59:4784–4787.PubMedGoogle Scholar
  59. 59.
    Moinova H, Leidner RS, Ravi L, et al. Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies. Cancer Epidemiol Biomark Prev. 2012;21:594–600.CrossRefGoogle Scholar
  60. 60.
    Yu M, O’Leary RM, Kaz AM, et al. Methylated B3GAT2 and ZNF793 are potential detection biomarkers for Barrett’s esophagus. Cancer Epidemiol Biomark Prev. 2015;24:1890–1897.CrossRefGoogle Scholar
  61. 61.
    Chettouh H, Mowforth O, Galeano-Dalmau N, et al. Methylation panel is a diagnostic biomarker for Barrett’s oesophagus in endoscopic biopsies and non-endoscopic cytology specimens. Gut. 2017.  https://doi.org/10.1136/gutjnl-2017-314026.PubMedCrossRefGoogle Scholar
  62. 62.
    Kaz AM, Luo Y, Dzieciatkowski S, et al. Aberrantly methylated PKP1 in the progression of Barrett’s esophagus to esophageal adenocarcinoma. Genes Chromosom Cancer. 2012;51:384–393.CrossRefPubMedGoogle Scholar
  63. 63.
    Kaz AM, Grady WM, Stachler MD, et al. Genetic and epigenetic alterations in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterol Clin N Am. 2015;44:473–489.CrossRefGoogle Scholar
  64. 64.
    Issa JP. Aging and epigenetic drift: a vicious cycle. J Clin Invest. 2014;124:24–29.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004;20:63–68.CrossRefPubMedGoogle Scholar
  66. 66.
    Li L, Li C, Mao H, et al. Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers. Sci Rep. 2016;6:26591.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Christensen KN, Fidler JL, Fletcher JG, et al. Pictorial review of colonic polyp and mass distortion and recognition with the CT virtual dissection technique. Radiographics. 2010;30:e42.CrossRefPubMedGoogle Scholar
  68. 68.
    Sontag LB, Lorincz MC, Georg Luebeck E. Dynamics, stability and inheritance of somatic DNA methylation imprints. J Theor Biol. 2006;242:890–899.CrossRefPubMedGoogle Scholar
  69. 69.
    Heyn H, Moran S, Esteller M. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome. Epigenetics. 2013;8:28–33.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49:359–367.CrossRefPubMedGoogle Scholar
  71. 71.
    Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Curtius K, Wong CJ, Hazelton WD, et al. A molecular clock infers heterogeneous tissue age among patients with Barrett’s esophagus. PLoS Comput Biol. 2016;12:e1004919.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Luebeck EG, Curtius K, Hazelton WD, et al. Identification of a key role of widespread epigenetic drift in Barrett’s esophagus and esophageal adenocarcinoma. Clin Epigenet. 2017;9:113.CrossRefGoogle Scholar
  74. 74.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297.CrossRefPubMedGoogle Scholar
  75. 75.
    Feber A, Xi L, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008;135:255–260. (discussion 260).CrossRefPubMedGoogle Scholar
  76. 76.
    Garman KS, Owzar K, Hauser ER, et al. MicroRNA expression differentiates squamous epithelium from Barrett’s esophagus and esophageal cancer. Dig Dis Sci. 2013;58:3178–3188.  https://doi.org/10.1007/s10620-013-2806-7.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Revilla-Nuin B, Parrilla P, Lozano JJ, et al. Predictive value of MicroRNAs in the progression of Barrett esophagus to adenocarcinoma in a long-term follow-up study. Ann Surg. 2013;257:886–893.CrossRefPubMedGoogle Scholar
  78. 78.
    Wu W, Bhagat TD, Yang X, et al. Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2013;144:956–966 e4.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Timmer MR, Sun G, Gorospe EC, et al. Predictive biomarkers for Barrett’s esophagus: so near and yet so far. Dis Esophagus. 2013;26:574–581.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Greenblatt MS, Bennett WP, Hollstein M, et al. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994;54:4855–4878.PubMedGoogle Scholar
  81. 81.
    Kaye PV, Haider SA, Ilyas M, et al. Barrett’s dysplasia and the Vienna classification: reproducibility, prediction of progression and impact of consensus reporting and p53 immunohistochemistry. Histopathology. 2009;54:699–712.CrossRefPubMedGoogle Scholar
  82. 82.
    Bird-Lieberman EL, Dunn JM, Coleman HG, et al. Population-based study reveals new risk-stratification biomarker panel for Barrett’s esophagus. Gastroenterology. 2012;143:927–935 e3.CrossRefPubMedGoogle Scholar
  83. 83.
    Skacel M, Petras RE, Rybicki LA, et al. p53 expression in low grade dysplasia in Barrett’s esophagus: correlation with interobserver agreement and disease progression. Am J Gastroenterol. 2002;97:2508–2513.CrossRefPubMedGoogle Scholar
  84. 84.
    Kaye PV, Haider SA, James PD, et al. Novel staining pattern of p53 in Barrett’s dysplasia–the absent pattern. Histopathology. 2010;57:933–935.CrossRefPubMedGoogle Scholar
  85. 85.
    Khan S, Do KA, Kuhnert P, et al. Diagnostic value of p53 immunohistochemistry in Barrett’s esophagus: an endoscopic study. Pathology. 1998;30:136–140.CrossRefPubMedGoogle Scholar
  86. 86.
    Murray L, Sedo A, Scott M, et al. TP53 and progression from Barrett’s metaplasia to oesophageal adenocarcinoma in a UK population cohort. Gut. 2006;55:1390–1397.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Bani-Hani K, Martin IG, Hardie LJ, et al. Prospective study of cyclin D1 overexpression in Barrett’s esophagus: association with increased risk of adenocarcinoma. J Natl Cancer Inst. 2000;92:1316–1321.CrossRefPubMedGoogle Scholar
  88. 88.
    Sikkema M, Kerkhof M, Steyerberg EW, et al. Aneuploidy and overexpression of Ki67 and p53 as markers for neoplastic progression in Barrett’s esophagus: a case-control study. Am J Gastroenterol. 2009;104:2673–2680.CrossRefPubMedGoogle Scholar
  89. 89.
    Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut. 2014;63:7–42.CrossRefPubMedGoogle Scholar
  90. 90.
    Li X, Galipeau PC, Paulson TG, et al. Temporal and spatial evolution of somatic chromosomal alterations: a case-cohort study of Barrett’s esophagus. Cancer Prev Res (Phila). 2014;7:114–127.CrossRefGoogle Scholar
  91. 91.
    Maley CC, Galipeau PC, Li X, et al. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res. 2004;64:7629–7633.CrossRefPubMedGoogle Scholar
  92. 92.
    Maley CC, Reid BJ, Forrest S. Cancer prevention strategies that address the evolutionary dynamics of neoplastic cells: simulating benign cell boosters and selection for chemosensitivity. Cancer Epidemiol Biomark Prev. 2004;13:1375–1384.Google Scholar
  93. 93.
    Maley CC, Reid BJ. Natural selection in neoplastic progression of Barrett’s esophagus. Semin Cancer Biol. 2005;15:474–483.CrossRefPubMedGoogle Scholar
  94. 94.
    Merlo LM, Shah NA, Li X, et al. A comprehensive survey of clonal diversity measures in Barrett’s esophagus as biomarkers of progression to esophageal adenocarcinoma. Cancer Prev Res (Phila). 2010;3:1388–1397.CrossRefGoogle Scholar
  95. 95.
    Reid BJ, Kostadinov R, Maley CC. New strategies in Barrett’s esophagus: integrating clonal evolutionary theory with clinical management. Clin Cancer Res. 2011;17:3512–3519.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of Internal MedicineUniversity of Washington School of MedicineSeattleUSA

Personalised recommendations