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Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression
  1. Beatriz Carvalho (b.carvalho{at}vumc.nl)
  1. VU University Medical Center, Netherlands
    1. Cindy Postma (c.postma{at}vumc.nl)
    1. VU University Medical Center, Netherlands
      1. Sandra Mongera (s.mongera{at}vumc.nl)
      1. VU University Medical Center, Netherlands
        1. Erik Hopmans (e.hopmans{at}vumc.nl)
        1. VU University Medical Center, Netherlands
          1. Sharon Diskin (diskin{at}email.chop.edu)
          1. University of Pennsylvania, United States
            1. Mark A. van de Wiel (mark.vdwiel{at}vumc.nl)
            1. VU University Medical Center, Netherlands
              1. Wim van Criekinge (wim.vancriekinge{at}ugent.be)
              1. Ghent University, Belgium
                1. Olivier Thas (olivier.thas{at}ugent.be)
                1. Ghent University, Belgium
                  1. Anja Matthäi (anja.matthaei{at}tu-dresden.de)
                  1. Technical University Dresden, Germany
                    1. Miguel A. Cuesta (ma.cuesta{at}vumc.nl)
                    1. VU University Medical Center, Netherlands
                      1. Jochim S. Terhaar sive Droste (js.terhaar{at}vumc.nl)
                      1. VU University Medical Center, Netherlands
                        1. Mikael Edward Craanen (me.craanen{at}vumc.nl)
                        1. VU University Medical Center, Netherlands
                          1. Evelin Schröck (evelin.schrock{at}mailbox.tu-dresden.de)
                          1. Technical University Dresden, Germany
                            1. Bauke Ylstra (b.ylstra{at}vumc.nl)
                            1. VU University Medical Center, Netherlands
                              1. Gerrit A. Meijer (ga.meijer{at}vumc.nl)
                              1. VU University Medical Center, Netherlands

                                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 in 34 non-progressed colorectal adenomas, 41 progressed adenomas (i.e. 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: Genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q were significantly overexpressed in carcinomas compared to adenomas as 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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