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Distinct oncogenes drive different genome and epigenome alterations in human mammary epithelial cells.
Fonti, Claire; Saumet, Anne; Abi-Khalil, Amanda; Orsetti, Béatrice; Cleroux, Elouan; Bender, Ambre; Dumas, Michael; Schmitt, Emeline; Colinge, Jacques; Jacot, William; Weber, Michael; Sardet, Claude; du Manoir, Stanislas; Theillet, Charles.
Afiliação
  • Fonti C; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Saumet A; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Abi-Khalil A; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Orsetti B; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Cleroux E; ICM, Institut Régional du Cancer de Montpellier, Montpellier, France.
  • Bender A; CNRS, University of Strasbourg, UMR 7242 Biotechnology and Cell Signaling, Strasbourg, France.
  • Dumas M; CNRS, University of Strasbourg, UMR 7242 Biotechnology and Cell Signaling, Strasbourg, France.
  • Schmitt E; CNRS, University of Strasbourg, UMR 7242 Biotechnology and Cell Signaling, Strasbourg, France.
  • Colinge J; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Jacot W; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Weber M; ICM, Institut Régional du Cancer de Montpellier, Montpellier, France.
  • Sardet C; CNRS, University of Strasbourg, UMR 7242 Biotechnology and Cell Signaling, Strasbourg, France.
  • du Manoir S; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
  • Theillet C; IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
Int J Cancer ; 145(5): 1299-1311, 2019 09 01.
Article em En | MEDLINE | ID: mdl-31093963
Molecular subtypes of breast cancer are defined on the basis of gene expression and genomic/epigenetic pattern differences. Different subtypes are thought to originate from distinct cell lineages, but the early activation of an oncogene could also play a role. It is difficult to discriminate the respective inputs of oncogene activation or cell type of origin. In this work, we wished to determine whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. To this aim, we transduced shp53 immortalized HMECs in parallel with the CCNE1, WNT1 and RASv12 oncogenes which activate distinct oncogenic pathways and characterized them at sequential stages of transformation for changes in their genetic and epigenetic profiles. We show that initial activation of CCNE1, WNT1 and RASv12, in shp53 HMECs results in different and reproducible changes in mRNA and micro-RNA expression, copy number alterations (CNA) and DNA methylation profiles. Noticeably, HMECs transformed by RAS bore very specific profiles of CNAs and DNA methylation, clearly distinct from those shown by CCNE1 and WNT1 transformed HMECs. Genes impacted by CNAs and CpG methylation in the RAS and the CCNE1/WNT1 clusters showed clear differences, illustrating the activation of distinct pathways. Our data show that early activation of distinct oncogenic pathways leads to active adaptive events resulting in specific sets of CNAs and DNA methylation changes. We, thus, propose that activation of different oncogenes could have a role in reshaping the genetic landscape of breast cancer subtypes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oncogenes / Neoplasias da Mama / Glândulas Mamárias Humanas Limite: Animals / Female / Humans Idioma: En Revista: Int J Cancer Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oncogenes / Neoplasias da Mama / Glândulas Mamárias Humanas Limite: Animals / Female / Humans Idioma: En Revista: Int J Cancer Ano de publicação: 2019 Tipo de documento: Article