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Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression
  1. B Carvalho1,
  2. C Postma1,
  3. S Mongera1,
  4. E Hopmans1,
  5. S Diskin2,3,4,
  6. M A van de Wiel1,5,6,
  7. W van Criekinge7,
  8. O Thas8,
  9. A Matthäi9,
  10. M A Cuesta10,
  11. J S Terhaar sive Droste11,
  12. M Craanen11,
  13. E Schröck9,
  14. B Ylstra1,
  15. G A Meijer1
  1. 1
    Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
  2. 2
    Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  3. 3
    Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  4. 4
    Penn Center for Bioinformatics (PCBI), University of Pennsylvania
  5. 5
    Department of Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  6. 6
    Department of Mathematics, Free University (VU), Amsterdam, The Netherlands
  7. 7
    Laboratory of Bioinformatics and Computational Genomics, Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
  8. 8
    Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Ghent, Belgium
  9. 9
    Technical University Dresden, Medical Faculty Carl Gustav Carus, Institute for Clinical Genetics, Dresden, Germany
  10. 10
    Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
  11. 11
    Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
  1. Dr G A Meijer, Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands; ga.meijer{at}vumc.nl

Abstract

Objective: This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon.

Methods: Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays.

Results: The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q.

Conclusion: This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.

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Footnotes

  • ▸ Additional tables and a figure are published online only at http://gut.bmj.com/content/vol58/issue1

  • Funding: This study was financially supported by the Dutch Cancer Society (KWF2002-2618).

  • Competing interests: None.

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