Skip to main content
SpringerLink
Log in

Genomics of Esophageal Cancer and Biomarkers for Early Detection

  • Chapter
  • First Online:
Book cover Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 908))

Abstract

In-depth molecular characterization of esophageal oncogenesis has improved over the recent years. Advancement in molecular biology and bioinformatics has led to better understanding of its genomic landscape. More specifically, analysis of its pathogenesis at the genetic level has uncovered the involvement of a number of tumor suppressor genes, cell cycle regulators, and receptor tyrosine kinases. Due to its poor prognosis, the development of clinically applicable biomarkers for diagnosis, progression, and treatment has been the focus of many research studies concentrating on upper gastrointestinal malignancies. As in other cancers, early detection and subsequent intervention of the preneoplastic condition significantly improves patient outcomes. Currently, clinically approved surveillance practices heavily depend on expensive, invasive, and sampling-error-prone endoscopic procedures. There is, therefore, a great demand to establish clearly reliable biomarkers that could identify those patients at higher risk of neoplastic progression and hence would greatly benefit from further monitoring and/or intervention. This chapter will present the most recent advances in the analysis of the esophageal cancer genome serving as basis for biomarker development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Montgomery EA, et al. Oesophageal cancer. In: Stewart BW, Wild CP. World Cancer Report 2014. World Health Organization; 2014. p. 528–543.

    Google Scholar 

  2. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013.

    Google Scholar 

  3. Cancer Research UK (CRUK) Oesophageal cancer. http://www.cancerresearchuk.org/cancer-help/type/oesophageal-cancer/. Accessed 31 Jan 2014.

  4. Spechler SJ. Barrett esophagus and risk of esophageal cancer: a clinical review. JAMA. 2013;310:627–36.

    Article  CAS  PubMed  Google Scholar 

  5. di Pietro M, Fitzgerald RC. Screening and risk stratification for Barrett’s esophagus: how to limit the clinical impact of the increasing incidence of esophageal adenocarcinoma. Gastroenterol Clin North Am. 2013;42(1):155–73. doi:10.1016/j.gtc.2012.11.006. Review.

    Article  PubMed  Google Scholar 

  6. Ali HR, Rueda OM, Chin SF, Curtis C, et al. Genome-driven integrated classification of breast cancer validated in over 7,500 samples. Genome Biol. 2014;15(8):431. doi:10.1186/s13059-014-0431-1.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Paul MK, Mukhopadhyay AK. Tyrosine kinase—role and significance in cancer. Int J Med Sci. 2004;1(2):101–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ekman S, Bergqvist M, Heldin CH, Lennartsson J. Activation of growth factor receptors in esophageal cancer—implications for therapy. Oncologist. 2007;12:1165–77. doi:10.1634/theoncologist.12-10-1165.

    Article  CAS  PubMed  Google Scholar 

  9. Kwak EL, Jankowski J, Thayer SP, Lauwers GY, Brannigan BW, Harris PL, Okimoto RA, Haserlat SM, Driscoll DR, Ferry D, Muir B, Settleman J, Fuchs CS, Kulke MH, Ryan DP, Clark JW, Sgroi DC, Haber DA, Bell DW. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res. 2006;12(14 Pt 1):4283–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gowryshankar A, Nagaraja V, Eslick GD. HER2 status in Barrett’s esophagus and esophageal cancer: a meta analysis. J Gastrointest Oncol. 2014;5(1):25–35. doi:10.3978/j.issn.2078-6891.2013.039.

    PubMed  PubMed Central  Google Scholar 

  11. Langer R, Rauser S, Feith M, Nährig JM, Feuchtinger A, Friess H, Höfler H, Walch A. Assessment of ErbB2 (Her2) in oesophageal adenocarcinomas: summary of a revised immunohistochemical evaluation system, bright field double in situ hybridisation and fluorescence in situ hybridisation. Mod Pathol. 2011;24(7):908–16. doi:10.1038/modpathol.2011.52.

    Article  CAS  PubMed  Google Scholar 

  12. Wei Q, Chen L, Sheng L, Nordgren H, Wester K, Carlsson J. EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases. Int J Oncol. 2007;31(3):493–9.

    PubMed  Google Scholar 

  13. Kim J, Fox C, Peng S, Pusung M, Pectasides E, Matthee E, Hong YS, Do IG, Jang J, Thorner AR, Van Hummelen P, Rustgi AK, Wong KK, Zhou Z, Tang P, Kim KM, Lee J, Bass AJ. Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma. J Clin Invest. 2014;124(12):5145–58. doi:10.1172/JCI75200.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Torquati A, O’rear L, Longobardi L, Spagnoli A, Richards WO, Daniel Beauchamp R. RUNX3 inhibits cell proliferation and induces apoptosis by reinstating transforming growth factor beta responsiveness in esophageal adenocarcinoma cells. Surgery. 2004;136(2):310–6.

    Article  PubMed  Google Scholar 

  15. Garrigue-Antar L, Souza RF, Vellucci VF, Meltzer SJ, Reiss M. Loss of transforming growth factor-beta type II receptor gene expression in primary human esophageal cancer. Lab Invest. 1996;75(2):263–72.

    CAS  PubMed  Google Scholar 

  16. Boonstra JJ, van Marion R, Douben HJ, Lanchbury JS, Timms KM, et al. Mapping of homozygous deletions in verified esophageal adenocarcinoma cell lines and xenografts. Genes Chromosomes Cancer. 2012;51(3):272–82.

    Article  CAS  PubMed  Google Scholar 

  17. Dulak AM, Stojanov P, Peng S, Lawrence MS, Fox C, et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet. 2013;45(5):478–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Weaver JM, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, et al. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Nat Genet. 2014;46(8):837–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Singhi AD, Foxwell TJ, Nason K, Cressman KL, McGrath KM, et al. Smad4 loss in esophageal adenocarcinoma is associated with an increased propensity for disease recurrence and poor survival. Am J Surg Pathol. 2015;39(4):487–95.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang Y, Qin X, Wu J, Qi B, Tao Y, et al. Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis. PLoS One. 2014;9(9):e107598.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Miller CT, Moy JR, Lin L, Schipper M, Normolle D, et al. Gene amplification in esophageal adenocarcinomas and Barrett’s with high-grade dysplasia. Clin Cancer Res. 2003;9(13):4819–25.

    CAS  PubMed  Google Scholar 

  22. Sarbia M, Arjumand J, Wolter M, et al. Frequent c-myc amplification in high-grade dysplasia and adenocarcinoma in Barrett esophagus. Am J Clin Pathol. 2001;115(6):835–40.

    Article  CAS  PubMed  Google Scholar 

  23. von Rahden BH, Stein HJ, Pühringer-Oppermann F, Sarbia M. c-myc amplification is frequent in esophageal adenocarcinoma and correlated with the upregulation of VEGF-A expression. Neoplasia. 2006;8(9):702–7.

    Article  CAS  Google Scholar 

  24. Lagorce C, Paraf F, Vidaud D, Couvelard A, Wendum D, et al. Cyclooxygenase-2 is expressed frequently and early in Barrett’s oesophagus and associated adenocarcinoma. Histopathology. 2003;42(5):457–65.

    Article  CAS  PubMed  Google Scholar 

  25. Prins MJ, Verhage RJ, ten Kate FJ, van Hillegersberg R. Cyclooxygenase isoenzyme-2 and vascular endothelial growth factor are associated with poor prognosis in esophageal adenocarcinoma. J Gastrointest Surg. 2012;16(5):956–66. doi:10.1007/s11605-011-1814-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Surget S, Khoury MP, Bourdon JC. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective. Onco Targets Ther. 2013;7:57–68. doi:10.2147/OTT.S53876.

    PubMed  PubMed Central  Google Scholar 

  27. Dolan K, Walker SJ, Gosney J, Field JK, Sutton R. TP53 mutations in malignant and premalignant Barrett’s esophagus. Dis Esophagus. 2003;16(2):83–9.

    Article  CAS  PubMed  Google Scholar 

  28. Reid BJ, Prevo LJ, Galipeau PC, Sanchez CA, Longton G, Levine DS, Blount PL, Rabinovitch PS. Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol. 2001;96(10):2839–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chung SM, Kao J, Hyjek E, Chen YT. p53 in esophageal adenocarcinoma: a critical reassessment of mutation frequency and identification of 72Arg as the dominant allele. Int J Oncol. 2007;31:1351–5.

    CAS  PubMed  Google Scholar 

  30. Galipeau PC, et al. Clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in premalignant esophageal (Barrett’s) tissue. J Natl Cancer Inst. 1999;91:2087–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Maley CC, Galipeau PC, Li X, Sanchez CA, Paulson TG, Reid BJ. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett’s esophagus. Cancer Res. 2004;64(10):3414–27.

    Article  CAS  PubMed  Google Scholar 

  32. Hardie LJ, et al. p16 expression in Barrett’s esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations. Cancer Lett. 2005;217:221–30.

    Article  CAS  PubMed  Google Scholar 

  33. Bian YS, Osterheld MC, Fontolliet C, Bosman FT, Benhattar J. p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett’s esophagus. Gastroenterology. 2002;122(4):1113–21.

    Article  CAS  PubMed  Google Scholar 

  34. Huang Y, Peters CJ, Fitzgerald RC, Gjerset RA. Progressive silencing of p14ARF in oesophageal adenocarcinoma. J Cell Mol Med. 2009;13:398–409.

    Article  CAS  PubMed  Google Scholar 

  35. Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, et al. Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis. Cancer Res. 2012;72(17):4383–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chow AY. Cell cycle control by oncogenes and tumor suppressors: driving the transformation of normal cells into cancerous cells. Nat Educ. 2010;3(9):7.

    Google Scholar 

  37. Geddert H, Heep HJ, Gabbert HE, et al. Expression of cyclin B1 in the metaplasia—dysplasia—carcinoma sequence of Barrett esophagus. Cancer. 2002;94:212–8.

    Article  CAS  PubMed  Google Scholar 

  38. Arber N, Gammon MD, Hibshoosh H, et al. Overexpression of cyclin D1 occurs in both squamous carcinomas and adenocarci- nomas of the esophagus and in adenocarcinomas of the stomach. Hum Pathol. 1999;30:1087–92.

    Article  CAS  PubMed  Google Scholar 

  39. Morgan RJ, Newcomb PV, Hardwick RH, Alderson D. Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma. Eur J Surg Oncol. 1999;25(4):364–7.

    Article  CAS  PubMed  Google Scholar 

  40. Sarbia M, Stahl M, Fink U, Heep H, Dutkowski P, Willers R, Seeber S, Gabbert HE. Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities. Int J Cancer. 1999;84(1):86–91.

    Article  CAS  PubMed  Google Scholar 

  41. Gu J, Ajani JA, Hawk ET, Ye Y, Lee JH, Bhutani MS, et al. Genomewide catalogue of chromosomal aberrations in Barrett’s esophagus and esophageal adenocarcinoma: a high-density single nucleotide polymorphism array analysis. Cancer Prev Res (Phila). 2010;3:1176–86.

    Article  CAS  Google Scholar 

  42. Semb H, Christofori G. The tumor-suppressor function of E-cadherin. Am J Hum Genet. 1998;63(6):1588–93. doi:10.1086/302173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Falkenback D, Nilbert M, Oberg S, Johansson J. Prognostic value of cell adhesion in esophageal adenocarcinomas. Dis Esophagus. 2008;21(2):97–102. doi:10.1111/j.1442-2050.2007.00749.x.

    Article  CAS  PubMed  Google Scholar 

  44. Bongiorno PF, Al-Kasspooles M, Lee SW, Rachwal WJ, Moore JH, Whyte RI, Orringer MB, Beer DG. E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett’s oesophagus. Br J Cancer. 1995;71(1):166–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Krishnadath KK, Tilanus HW, van Blankenstein M, Hop WC, Kremers ED, Dinjens WN, Bosman FT. Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. J Pathol. 1997;182(3):331–8.

    Article  CAS  PubMed  Google Scholar 

  46. Schauer MC, Stoecklein NH, Theisen J, Kröpil F, Baldus S, Hoelscher A, Feith M, Bölke E, Matuschek C, Budach W, Knoefel WT. The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging. Eur J Med Res. 2012;17:10. doi:10.1186/2047-783X-17-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pinto D, Gregorieff A, Begthel H, Clevers H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 2003;17(14):1709–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 2010;15(2):117–34. doi:10.1007/s10911-010-9178-9. Epub 2010 May 19.

    Article  PubMed  PubMed Central  Google Scholar 

  49. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26. doi:10.1016/j.devcel.2009.06.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Moyes LH, McEwan H, Radulescu S, Pawlikowski J, Lamm CG, Nixon C, Sansom OJ, Going JJ, Fullarton GM, Adams PD. Activation of Wnt signalling promotes development of dysplasia in Barrett’s oesophagus. J Pathol. 2012;228(1):99–112. doi:10.1002/path.4058.

    CAS  PubMed  Google Scholar 

  51. Clément G, Braunschweig R, Pasquier N, Bosman FT, Benhattar J. Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett’s esophagus. Oncogene. 2006;25(21):3084–92.

    Article  PubMed  CAS  Google Scholar 

  52. Galipeau PC, Cowan DS, Sanchez CA, et al. 17p (p53) allelic losses, 4N (G2/tetraploid) populations and progression to aneuploidy in Barrett’s oesophagus. Proc Natl Acad Sci U S A. 1996;93:7081–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Reid BJ, Haggit RC, Rubin CE, Rabinovitch PS. Barrett’s esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology. 1987;93(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  54. Flejou JF, Doublet B, Potet F, Metayer J, Hemet J. DNA ploidy in adenocarcinoma of Barrett’s esophagus. Ann Pathol. 1990;10:161–5.

    CAS  PubMed  Google Scholar 

  55. Yu C, Zhang X, Huang Q, Klein M, Goyal RK. High-fidelity DNA histograms in neoplastic progression in Barrett’s esophagus. Lab Invest. 2007;87(5):466–72.

    Article  CAS  PubMed  Google Scholar 

  56. Zhang X, Huang Q, Goyal RK, Odze RD. DNA ploidy abnormalities in basal and superficial regions of the crypts in Barrett’s esophagus and associated neoplastic lesions. Am J Surg Pathol. 2008;32(9):1327–35.

    Article  PubMed  Google Scholar 

  57. Nones K, Waddell N, Wayte N, Patch AM, Bailey P, Newell F, Holmes O, Fink JL, Quinn MC, Tang YH, Lampe G, Quek K, Loffler KA, Manning S, Idrisoglu S, Miller D, Xu Q, Waddell N, Wilson PJ, Bruxner TJ, Christ AN, Harliwong I, Nourse C, Nourbakhsh E, Anderson M, Kazakoff S, Leonard C, Wood S, Simpson PT, Reid LE, Krause L, Hussey DJ, Watson DI, Lord RV, Nancarrow D, Phillips WA, Gotley D, Smithers BM, Whiteman DC, Hayward NK, Campbell PJ, Pearson JV, Grimmond SM, Barbour AP. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun. 2014;5:5224. doi:10.1038/ncomms6224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Turnpenny P, Ellard S. Emery’s elements of medical genetics. 12th ed. London: Elsevier; 2005.

    Google Scholar 

  59. Peltomäki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003;21(6):1174–9.

    Article  PubMed  CAS  Google Scholar 

  60. Koppert LB, Wijnhoven BP, van Dekken H, et al. The molecular biology of esophageal adenocarcinoma. J Surg Oncol. 2005;92:169–90.

    Article  CAS  PubMed  Google Scholar 

  61. Evans SC, Gillis A, Geldenhuys L, et al. Microsatellite instability in esophageal adenocarcinoma. Cancer Lett. 2004;212:241–51.

    Article  CAS  PubMed  Google Scholar 

  62. Meltzer SJ, Yin J, Manin B, Rhyu MG, Cottrell J, Hudson E, Redd JL, Krasna MJ, Abraham JM, Reid BJ. Microsatellite instability occurs frequently and in both diploid and aneuploid cell populations of Barrett’s-associated esophageal adenocarcinomas. Cancer Res. 1994;54:3379–82.

    CAS  PubMed  Google Scholar 

  63. Gleeson CM, Sloan JM, McGuigan JA, Ritchie AJ, Weber JL, Russell SHE. Ubiquitous somatic alterations at microsatellite alleles occur infrequently in Barrett’s-associated esophageal adenocarcinomas. Cancer Res. 1996;56:259–63.

    CAS  PubMed  Google Scholar 

  64. Khara HS, Jackson SA, Nair S, Deftereos G, Patel S, Silverman JF, Ellsworth E, Sumner C, Corcoran B, Smith Jr DM, Finkelstein S, Gross SA. Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett’s esophagus. J Gastrointest Cancer. 2014;45(2):137–45. doi:10.1007/s12029-013-9570-y.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ellsworth E, Jackson SA, Thakkar SJ, Smith Jr DM, Finkelstein S. Correlation of the presence and extent of loss of heterozygosity mutations with histological classifications of Barrett’s esophagus. BMC Gastroenterol. 2012;12(1):181. doi:10.1186/1471-230X-12-181.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9. doi:10.1038/nature13480.

    Article  CAS  Google Scholar 

  67. Saldivar JC, Shibata H, Huebner K. Pathology and biology associated with the fragile FHIT gene and gene product. J Cell Biochem. 2010;109(5):858–65.

    CAS  PubMed  Google Scholar 

  68. Hu B, Han SY, Wang X, Ottey M, Potoczek MB, Dicker A, Huebner K, Wang Y. Involvement of the Fhit gene in the ionizing radiation-activated ATR/CHK1 pathway. J Cell Physiol. 2005;202(2):518–23.

    Article  CAS  PubMed  Google Scholar 

  69. Ishii H, Mimori K, Ishikawa K, Okumura H, Pichiorri F, Druck T, Inoue H, Vecchione A, Saito T, Mori M, Huebner K. Fhit-deficient hematopoietic stem cells survive hydroquinone exposure carrying precancerous changes. Cancer Res. 2008;68(10):3662–70. doi:10.1158/0008-5472.CAN-07-5687.

    Article  CAS  PubMed  Google Scholar 

  70. Ohta M, Inoue H, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Croce CM, Huebner K, The FHIT. Gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell. 1996;84(4):587–97.

    Article  CAS  PubMed  Google Scholar 

  71. Mori M, Mimori K, Shiraishi T, Alder H, Inoue H, Tanaka Y, Sugimachi K, Huebner K, Croce CM. Altered expression of Fhit in carcinoma and precarcinomatous lesions of the esophagus. Cancer Res. 2000;60(5):1177–82.

    CAS  PubMed  Google Scholar 

  72. Lai LA, Kostadinov R, Barrett MT, Peiffer DA, Pokholok D, Odze R, Sanchez CA, Maley CC, Reid BJ, Gunderson KL, Rabinovitch PS. Deletion at fragile sites is a common and early event in Barrett’s esophagus. Mol Cancer Res. 2010;8(8):1084–94. doi:10.1158/1541-7786.MCR-09-0529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chen YJ, Chen PH, Lee MD, Chang JG. Aberrant FHIT transcripts in cancerous and corresponding non-cancerous lesions of the digestive tract. Int J Cancer. 1997;72(6):955–8.

    Article  CAS  PubMed  Google Scholar 

  74. Wiech T, Nikolopoulos E, Weis R, Langer R, Bartholomé K, Timmer J, Walch AK, Höfler H, Werner M. Genome-wide analysis of genetic alterations in Barrett’s adenocarcinoma using single nucleotide polymorphism arrays. Lab Invest. 2009;89(4):385–97. doi:10.1038/labinvest.2008.67.

    Article  CAS  PubMed  Google Scholar 

  75. Frankel A, Armour N, Nancarrow D, Krause L, Hayward N, Lampe G, Smithers BM, Barbour A. Genome-wide analysis of esophageal adenocarcinoma yields specific copy number aberrations that correlate with prognosis. Genes Chromosomes Cancer. 2014;53(4):324–38. doi:10.1002/gcc.22143.

    Article  CAS  PubMed  Google Scholar 

  76. Davison JM, Yee M, Krill-Burger JM, Lyons-Weiler MA, Kelly LA, Sciulli CM, Nason KS, Luketich JD, Michalopoulos GK, LaFramboise WA. The degree of segmental aneuploidy measured by total copy number abnormalities predicts survival and recurrence in superficial gastroesophageal adenocarcinoma. PLoS One. 2014;9(1):e79079. doi:10.1371/journal.pone.0079079.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Chava S, Mohan V, Shetty PJ, Manolla ML, Vaidya S, Khan IA, Waseem GL, Boddala P, Ahuja YR, Hasan Q. Immunohistochemical evaluation of p53, FHIT, and IGF2 gene expression in esophageal cancer. Dis Esophagus. 2012;25(1):81–7. doi:10.1111/j.1442-2050.2011.01213.x.

    Article  CAS  PubMed  Google Scholar 

  78. Chen S-J, Huang S-S, Chang N-S. Role of WWOX and NF-kB in lung cancer progression. Transl Respir Med. 2013;1(1):15.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Aqeilan RI, Hagan JP, de Bruin A, Rawahneh M, Salah Z, Gaudio E, Siddiqui H, Volinia S, Alder H, Lian JB, Stein GS, Croce CM. Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis. Endocrinology. 2009;150(3):1530–5. doi:10.1210/en.2008-1087.

    Article  CAS  PubMed  Google Scholar 

  80. Abu-Odeh M, Bar-Mag T, Huang H, Kim T, Salah Z, Abdeen SK, Sudol M, Reichmann D, Sidhu S, Kim PM, Aqeilan RI. Characterizing WW domain interactions of tumor suppressor WWOX reveals its association with multiprotein networks. J Biol Chem. 2014;289(13):8865–80. doi:10.1074/jbc.M113.506790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Nancarrow DJ, Handoko HY, Smithers BM, Gotley DC, Drew PA, Watson DI, Clouston AD, Hayward NK, Whiteman DC. Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays. Cancer Res. 2008;68(11):4163–72. doi:10.1158/0008-5472.CAN-07-6710.

    Article  CAS  PubMed  Google Scholar 

  82. Shammas MA, Koley H, Beer DG, Li C, Goyal RK, Munshi NC. Growth arrest, apoptosis, and telomere shortening of Barrett’s-associated adenocarcinoma cells by a telomerase inhibitor. Gastroenterology. 2004;126(5):1337–46.

    Article  CAS  PubMed  Google Scholar 

  83. Lord RV, Salonga D, Danenberg KD, Peters JH, DeMeester TR, Park JM, Johansson J, Skinner KA, Chandrasoma P, DeMeester SR, Bremner CG, Tsai PI, Danenberg PV. Telomerase reverse transcriptase expression is increased early in the Barrett’s metaplasia, dysplasia, adenocarcinoma sequence. J Gastrointest Surg. 2000;4(2):135–42.

    Article  CAS  PubMed  Google Scholar 

  84. Morales CP, Lee EL, Shay JW. In situ hybridization for the detection of telomerase RNA in the progression from Barrett’s esophagus to esophageal adenocarcinoma. Cancer. 1998;83(4):652–9.

    Article  CAS  PubMed  Google Scholar 

  85. Cerone MA, Londono-Vallejo JA, Bacchetti S. Telomere maintenance by telomerase and by recombination can coexist in human cells. Hum Mol Genet. 2001;10(18):1945–52.

    Article  CAS  PubMed  Google Scholar 

  86. Verdun RE, Karlseder J. The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell. 2006;127(4):709–20.

    Article  CAS  PubMed  Google Scholar 

  87. Finley JC, Reid BJ, Odze RD, Sanchez CA, Galipeau P, Li X, Self SG, Gollahon KA, Blount PL, Rabinovitch PS. Chromosomal instability in Barrett’s esophagus is related to telomere shortening. Cancer Epidemiol Biomarkers Prev. 2006;15(8):1451–7.

    Article  CAS  PubMed  Google Scholar 

  88. Blackburn EH. Structure and function of telomeres. Nature. 1991;350(6319):569–73.

    Article  CAS  PubMed  Google Scholar 

  89. Mathieu N, Pirzio L, Freulet-Marrière MA, Desmaze C, Sabatier L. Telomeres and chromosomal instability. Cell Mol Life Sci. 2004;61(6):641–56.

    Article  CAS  PubMed  Google Scholar 

  90. Rodier F, Kim SH, Nijjar T, Yaswen P, Campisi J. Cancer and aging: the importance of telomeres in genome maintenance. Int J Biochem Cell Biol. 2005;37(5):977–90.

    Article  CAS  PubMed  Google Scholar 

  91. Pal J, Bertheau R, Buon L, Qazi A, Batchu RB, Bandyopadhyay S, Ali-Fehmi R, Beer DG, Weaver DW, Shmookler Reis RJ, Goyal RK, Huang Q, Munshi NC, Shammas MA. Genomic evolution in Barrett’s adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome. Oncogene. 2011;30(33):3585–98. doi:10.1038/onc.2011.83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lu R, Pal J, Buon L, Nanjappa P, Shi J, Fulciniti M, Tai YT, Guo L, Yu M, Gryaznov S, Munshi NC, Shammas MA. Targeting homologous recombination and telomerase in Barrett’s adenocarcinoma: impact on telomere maintenance, genomic instability and tumor growth. Oncogene. 2014;33(12):1495–505. doi:10.1038/onc.2013.103.

    Article  CAS  PubMed  Google Scholar 

  93. Monkhouse SJW, Muhlschlegel J, Barr H. Biomarkers in esophageal adenocarcinoma. Cancer biomarkers: minimal and noninvasive early diagnosis and prognosis. 2014. p. 321.

    Google Scholar 

  94. Wong DJ, Barrett MT, Stöger R, Emond MJ, Reid BJ. p16INK4a promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. Cancer Res. 1997;57:2619–22.

    CAS  PubMed  Google Scholar 

  95. Paulson TG, Galipeau PC, Xu L, Kissel HD, Li X, et al. p16 mutation spectrum in the premalignant condition Barrett’s esophagus. PLoS One. 2008;3(11):e3809. PubMed PMID: 19043591, PubMed Central PMCID: PMC2585012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Agarwal A, Polineni R, Hussein Z, Vigoda I, Bhagat TD, Bhattacharyya S, Maitra A, Verma A. Role of epigenetic alterations in the pathogenesis of Barrett’s esophagus and esophageal adenocarcinoma. Int J Clin Exp Pathol. 2012;5(5):382–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, Yin J, Fleisher AS, Abraham JM, Beer DG, Sidransky D, Huss HT, Demeester TR, Eads C, Laird PW, Ilson DH, Kelsen DP, Harpole D, Moore MB, Danenberg KD, Danenberg PV, Meltzer SJ. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst. 2000;92(22):1805–11.

    Article  CAS  PubMed  Google Scholar 

  98. Eads CA, Lord RV, Kurumboor SK, Wickramasinghe K, Skinner ML, Long TI, Peters JH, DeMeester TR, Danenberg KD, Danenberg PV, Laird PW, Skinner KA. Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Cancer Res. 2000;60(18):5021–6.

    CAS  PubMed  Google Scholar 

  99. Hamilton JP, Sato F, Jin Z, Greenwald BD, Ito T, Mori Y, Paun BC, Kan T, Cheng Y, Wang S, Yang J, Abraham JM, Meltzer SJ. Reprimo methylation is a potential biomarker of Barrett’s-associated esophageal neoplastic progression. Clin Cancer Res. 2006;12(22):6637–42.

    Article  CAS  PubMed  Google Scholar 

  100. Alvarez H, Opalinska J, Zhou L, Sohal D, Fazzari MJ, Yu Y, Montagna C, Montgomery EA, Canto M, Dunbar KB, Wang J, Roa JC, Mo Y, Bhagat T, Ramesh KH, Cannizzaro L, Mollenhauer J, Thompson RF, Suzuki M, Meltzer SJ, Melnick A, Greally JM, Maitra A, Verma A. Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis. PLoS Genet. 2011;7(3):e1001356. doi: 10.1371/journal.pgen.1001356. Epub 2011 Mar 31. Erratum in: PLoS Genet. 2011;7(5).

    Google Scholar 

  101. Wu W, Bhagat TD, Yang X, Song JH, Cheng Y, Agarwal R, Abraham JM, Ibrahim S, Bartenstein M, Hussain Z, Suzuki M, Yu Y, Chen W, Eng C, Greally J, Verma A, Meltzer SJ. Hypomethylation of noncoding DNA regions and overexpression of the long noncoding RNA, AFAP1-AS1, in Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterology. 2013;144(5):956–966.e4. doi:10.1053/j.gastro.2013.01.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M, Swanson SJ, Godfrey TE, Litle VR. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008;135(2):255–60. doi:10.1016/j.jtcvs.2007.08.055. discussion 260.

    Article  CAS  PubMed  Google Scholar 

  103. Garman KS, Owzar K, Hauser ER, Westfall K, Anderson BR, Souza RF, Diehl AM, Provenzale D, Shaheen NJ. MicroRNA expression differentiates squamous epithelium from Barrett’s esophagus and esophageal cancer. Dig Dis Sci. 2013;58(11):3178–88. doi:10.1007/s10620-013-2806-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Mathé EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, Braun R, Reimers M, Kumamoto K, Hughes D, Altorki NK, Casson AG, Liu CG, Wang XW, Yanaihara N, Hagiwara N, Dannenberg AJ, Miyashita M, Croce CM, Harris CC. MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res. 2009;15(19):6192–200. doi:10.1158/1078-0432.CCR-09-1467.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Leidner RS, Ravi L, Leahy P, Chen Y, Bednarchik B, Streppel M, Canto M, Wang JS, Maitra A, Willis J, Markowitz SD, Barnholtz-Sloan J, Adams MD, Chak A, Guda K. The microRNAs, MiR-31 and MiR-375, as candidate markers in Barrett’s esophageal carcinogenesis. Genes Chromosomes Cancer. 2012;51(5):473–9. doi:10.1002/gcc.21934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Fassan M, Volinia S, Palatini J, Pizzi M, Baffa R, De Bernard M, Battaglia G, Parente P, Croce CM, Zaninotto G, Ancona E, Rugge M. MicroRNA expression profiling in human Barrett’s carcinogenesis. Int J Cancer. 2011;129(7):1661–70. doi:10.1002/ijc.25823. Epub 2011 Mar 11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Revilla-Nuin B, Parrilla P, Lozano JJ, de Haro LF, Ortiz A, Martínez C, Munitiz V, de Angulo DR, Bermejo J, Molina J, Cayuela ML, Yélamos J. Predictive value of MicroRNAs in the progression of barrett esophagus to adenocarcinoma in a long-term follow-up study. Ann Surg. 2013;257(5):886–93. doi:10.1097/SLA.0b013e31826ddba6.

    Article  PubMed  Google Scholar 

  108. Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y. Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res. 2011;17(9):3029–38. doi:10.1158/1078-0432.CCR-10-2532.

    Article  CAS  PubMed  Google Scholar 

  109. Macha MA, Seshacharyulu P, Krishn SR, Pai P, Rachagani S, Jain M, et al. MicroRNAs (miRNA) as biomarker(s) for prognosis and diagnosis of gastrointestinal (GI) cancers. Curr Pharm Design. 2014;20(33):5287–97.

    Article  CAS  Google Scholar 

  110. Sakai NS, Samia-Aly E, Barbera M, Fitzgerald RC. A review of the current understanding and clinical utility of miRNAs in esophageal cancer. Semin Cancer Biol. 2013;23(6 Pt B):512–21. doi:10.1016/j.semcancer.2013.08.005.

    Article  CAS  PubMed  Google Scholar 

  111. Varghese S, Lao-Sirieix P, Fitzgerald RC. Identification and clinical implementation of biomarkers for Barrett’s esophagus. Gastroenterology. 2012;142(3):435–441.e2. doi:10.1053/j.gastro.2012.01.013.

    Article  PubMed  Google Scholar 

  112. Srivastava S. Cancer biomarker discovery and development in gastrointestinal cancers: early detection research network-a collaborative approach. Gastrointest Cancer Res. 2007;1(4 Suppl 2):S60–3.

    PubMed  PubMed Central  Google Scholar 

  113. Fouad YM, Mostafa I, Yehia R, El-Khayat H. Biomarkers of Barrett’s esophagus. World J Gastrointest Pathophysiol. 2014;5(4):450–6. doi:10.4291/wjgp.v5.i4.450.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Davelaar AL, Calpe S, Lau L, Timmer MR, Visser M, Ten Kate FJ, Parikh KB, Meijer SL, Bergman JJ, Fockens P, Krishnadath KK. Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett’s esophagus progression prediction: a prospective follow-up study. Genes Chromosomes Cancer. 2015;54(2):82–90. doi:10.1002/gcc.22220.

    Article  CAS  PubMed  Google Scholar 

  115. Sato F, Jin Z, Schulmann K, Wang J, Greenwald BD, Ito T, Kan T, Hamilton JP, Yang J, Paun B, David S, Olaru A, Cheng Y, Mori Y, Abraham JM, Yfantis HG, Wu TT, Fredericksen MB, Wang KK, Canto M, Romero Y, Feng Z, Meltzer SJ. Three-tiered risk stratification model to predict progression in Barrett’s esophagus using epigenetic and clinical features. PLoS One. 2008;3(4):e1890. doi:10.1371/journal.pone.0001890.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Jin Z, Cheng Y, Gu W, Zheng Y, Sato F, Mori Y, Olaru AV, Paun BC, Yang J, Kan T, Ito T, Hamilton JP, Selaru FM, Agarwal R, David S, Abraham JM, Wolfsen HC, Wallace MB, Shaheen NJ, Washington K, Wang J, Canto MI, Bhattacharyya A, Nelson MA, Wagner PD, Romero Y, Wang KK, Feng Z, Sampliner RE, Meltzer SJ. A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett’s esophagus. Cancer Res. 2009;69(10):4112–5. doi:10.1158/0008-5472.CAN-09-0028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Alvi MA, Liu X, O’Donovan M, Newton R, Wernisch L, Shannon NB, Shariff K, di Pietro M, Bergman JJ, Ragunath K, Fitzgerald RC. DNA methylation as an adjunct to histopathology to detect prevalent, inconspicuous dysplasia and early-stage neoplasia in Barrett’s esophagus. Clin Cancer Res. 2013;19(4):878–88. doi:10.1158/1078-0432.CCR-12-2880.

    Article  CAS  PubMed  Google Scholar 

  118. Hardikar S, Onstad L, Song X, Wilson AM, Montine TJ, et al. Inflammation and oxidative stress markers and esophageal adenocarcinoma incidence in a Barrett’s esophagus cohort. Cancer Epidemiol Biomarkers Prev. 2014;23(11):2393–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Galipeau PC, Li X, Blount PL, Maley CC, Sanchez CA, Odze RD, Ayub K, Rabinovitch PS, Vaughan TL, Reid BJ. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med. 2007;4(2):e67.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Kostadinov RL, Kuhner MK, Li X, Sanchez CA, Galipeau PC, Paulson TG, Sather CL, Srivastava A, Odze RD, Blount PL, Vaughan TL, Reid BJ, Maley CC. NSAIDs modulate clonal evolution in Barrett’s esophagus. PLoS Genet. 2013;9(6):e1003553. doi:10.1371/journal.pgen.1003553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bird-Lieberman EL, Dunn JM, Coleman HG, Lao-Sirieix P, Oukrif D, Moore CE, Varghese S, Johnston BT, Arthur K, McManus DT, Novelli MR, O’Donovan M, Cardwell CR, Lovat LB, Murray LJ, Fitzgerald RC. Population-based study reveals new risk-stratification biomarker panel for Barrett’s esophagus. Gastroenterology. 2012;143(4):927–35.e3. doi:10.1053/j.gastro.2012.06.041.

    Article  CAS  PubMed  Google Scholar 

  122. di Pietro M, Boerwinkel DF, Shariff MK, Liu X, Telakis E, Lao-Sirieix P, Walker E, Couch G, Mills L, Nuckcheddy-Grant T, Slininger S, O’Donovan M, Visser M, Meijer SL, Kaye PV, Wernisch L, Ragunath K, Bergman JJ, Fitzgerald RC. The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett’s oesophagus. Gut. 2015;64(1):49–56. doi:10.1136/gutjnl-2013-305975.

    Article  PubMed  Google Scholar 

  123. Bennett M, Mashimo H. Molecular markers and imaging tools to identify malignant potential in Barrett’s esophagus. World J Gastrointest Pathophysiol. 2014;5(4):438–49. doi:10.4291/wjgp.v5.i4.438.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Yates M, Cheong E, Luben R, Igali L, Fitzgerald R, Khaw KT, Hart A. Body mass index, smoking, and alcohol and risks of Barrett’s esophagus and esophageal adenocarcinoma: a UK prospective cohort study. Dig Dis Sci. 2014;59(7):1552–9. doi:10.1007/s10620-013-3024-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Duggan C, Onstad L, Hardikar S, Blount PL, Reid BJ, Vaughan TL. Association between markers of obesity and progression from Barrett’s esophagus to esophageal adenocarcinoma. Clin Gastroenterol Hepatol. 2013;11(8):934–43. doi:10.1016/j.cgh.2013.02.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Keszei AP, Schouten LJ, Driessen AL, Huysentruyt CJ, Keulemans YC, Goldbohm RA, van den Brandt PA. Vegetable, fruit and nitrate intake in relation to the risk of Barrett’s oesophagus in a large Dutch cohort. Br J Nutr. 2014;111(8):1452–62. doi:10.1017/S0007114513003929.

    Article  CAS  PubMed  Google Scholar 

  127. Lao-Sirieix P, Boussioutas A, Kadri SR, O’Donovan M, Debiram I, Das M, Harihar L, Fitzgerald RC. Non-endoscopic screening biomarkers for Barrett’s oesophagus: from microarray analysis to the clinic. Gut. 2009;58(11):1451–9. doi:10.1136/gut.2009.180281.

    Article  CAS  PubMed  Google Scholar 

  128. Ross-Innes CS, Debiram-Beecham I, O’Donovan M, Walker E, Varghese S, Lao-Sirieix P, Lovat L, Griffin M, Ragunath K, Haidry R, Sami SS, Kaye P, Novelli M, Disep B, Ostler R, Aigret B, North BV, Bhandari P, Haycock A, Morris D, Attwood S, Dhar A, Rees C, Rutter MD, Sasieni PD, Fitzgerald RC, BEST2 Study Group. Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett’s esophagus: a multi-center case-control study. PLoS Med. 2015;12(1):e1001780. doi:10.1371/journal.pmed.1001780.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Bansal A, Lee IH, Hong X, Mathur SC, Tawfik O, Rastogi A, Buttar N, Visvanathan M, Sharma P, Christenson LK. Discovery and validation of Barrett’s esophagus microRNA transcriptome by next generation sequencing. PLoS One. 2013;8(1):e54240. doi:10.1371/journal.pone.0054240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Vega KJ, May R, Sureban SM, Lightfoot SA, Qu D, Reed A, Weygant N, Ramanujam R, Souza R, Madhoun M, Whorton J, Anant S, Meltzer SJ, Houchen CW. Identification of the putative intestinal stem cell marker doublecortin and CaM kinase-like-1 in Barrett’s esophagus and esophageal adenocarcinoma. J Gastroenterol Hepatol. 2012;27(4):773–80. doi:10.1111/j.1440-1746.2011.06928.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Whorton J, Sureban SM, May R, Qu D, Lightfoot SA, Madhoun M, Johnson M, Tierney WM, Maple JT, Vega KJ, Houchen CW. DCLK1 is detectable in plasma of patients with Barrett’s esophagus and esophageal adenocarcinoma. Dig Dis Sci. 2015;60(2):509–13. doi:10.1007/s10620-014-3347-4.

    Article  CAS  PubMed  Google Scholar 

  132. Ahmad J, Arthur K, Maxwell P, Kennedy A, Johnston BT, Murray L, McManus DT. A cross sectional study of p504s, CD133, and Twist expression in the esophageal metaplasia dysplasia adenocarcinoma sequence. Dis Esophagus. 2015;28(3):276–82. doi:10.1111/dote.12181.

    Article  CAS  PubMed  Google Scholar 

  133. Howlader N, Noone AM, Krapcho M, et al., editors. SEER cancer statistics review. Bethesda, MD: National Cancer Institute; 1975–2010.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Cancer Unit, University of Cambridge, Cambridge, UK

    Mark Pusung, Sebastian Zeki & Rebecca Fitzgerald

Authors
  1. Mark Pusung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastian Zeki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebecca Fitzgerald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rebecca Fitzgerald .

Editor information

Editors and Affiliations

  1. UCL Cancer Institute, University College London, London, United Kingdom

    Marnix Jansen

  2. Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom

    Nicholas A. Wright

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Pusung, M., Zeki, S., Fitzgerald, R. (2016). Genomics of Esophageal Cancer and Biomarkers for Early Detection. In: Jansen, M., Wright, N. (eds) Stem Cells, Pre-neoplasia, and Early Cancer of the Upper Gastrointestinal Tract. Advances in Experimental Medicine and Biology, vol 908. Springer, Cham. https://doi.org/10.1007/978-3-319-41388-4_12

Download citation

Publish with us

Policies and ethics

Search

Navigation