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Genome-Wide Dna Methylation Profiling of Esophageal Squamous Cell Carcinoma From Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers Publisher Pubmed



Talukdar FR1 ; Lima SCS2 ; Khoueiry R1 ; Laskar RS1 ; Cuenin C1 ; Sorroche BP1, 3 ; Boisson AC1 ; Abediardekani B1 ; Carreira C1 ; Menya D4 ; Dzamalala CP5 ; Assefa M6 ; Aseffa A7 ; Mirandagoncalves V8 Show All Authors
Authors
  1. Talukdar FR1
  2. Lima SCS2
  3. Khoueiry R1
  4. Laskar RS1
  5. Cuenin C1
  6. Sorroche BP1, 3
  7. Boisson AC1
  8. Abediardekani B1
  9. Carreira C1
  10. Menya D4
  11. Dzamalala CP5
  12. Assefa M6
  13. Aseffa A7
  14. Mirandagoncalves V8
  15. Jeronimo C8
  16. Henrique RM8
  17. Shakeri R9
  18. Malekzadeh R9
  19. Gasmelseed N10
  20. Ellaithi M11
  21. Gangane N12
  22. Middleton DRS1
  23. Le Calvezkelm F1
  24. Ghantous A1
  25. Roux ML1
  26. Schuz J1
  27. Mccormack V1
  28. Parker MI13
  29. Pinto LFR2
  30. Herceg Z1
Show Affiliations
Authors Affiliations
  1. 1. International Agency for Research on Cancer, Lyon, France
  2. 2. Department of Molecular Carcinogenesis, Brazilian National Cancer Institute, Rio de Janeiro, Brazil
  3. 3. Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
  4. 4. Moi University, Eldoret, Kenya
  5. 5. University of Malawi, Blantyre, Malawi
  6. 6. Addis Ababa University, Addis Ababa, Ethiopia
  7. 7. Armauer Hansen Research Institute, Addis Ababa, Ethiopia
  8. 8. Department of Pathology and Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto, Biomedical Sciences Institute, University of Porto, Porto, Portugal
  9. 9. Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Molecular Biology, National Cancer Institute, University of Gezira, Gezira, Sudan
  11. 11. Department of Histopathology and Cytology, Al-Neelain University, Khartoum, Sudan
  12. 12. Mahatma Gandhi Institute of Medical Sciences, Sevagram, India
  13. 13. Integrative Biomedical Sciences and IDM, University of Cape Town, Cape Town, South Africa

Source: Cancer Research Published:2021


Abstract

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumorspecific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and SouthAmerica. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Db) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. © 2021 American Association for Cancer Research.
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