BioProject

Gene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications constitute the bases of molecular classification of breast cancer. More...

Gene expression differences, combined with distinct patterns of genomic rearrangements and epigenetic modifications constitute the bases of molecular classification of breast cancer. Molecular subtypes may originate from different cell lineages in the mammary gland, but also from the early activation of oncogenes that may drive the establishment of these molecular subtypes. However, in the natural history of human cancer, it is difficult to discriminate between these two factors : cell lineage and initial oncogenic alterations. In this work, we designed an experimental strategy aiming at determining whether activation of distinct oncogenic pathways in human mammary epithelial cells (HMEC) could lead to different patterns of genetic and epigenetic changes. This work suggests that the early activation of oncogenes is an important determinant of the establishment of breast cancer molecular subtypes along with cell lineage origin. In this work, we overexpressed by retroviral transduction three oncogenes WNT1, CCNE1 and RASv12, known to activate different oncogenic pathways, in shp53 immortalized human HMECs and monitored epigenetic and genetic changes at different steps of cell progression.Submitted publication : Distinct Oncogenic events induces different DNA methylation and copy number changes in human mammary epithelial cells.Claire Fonti, Anne Saumet, Amanda Abi-Khalil, Béatrice Orsetti,..., J. Colinge, Michael Weber, Claude Sardet, Stanislas du Manoir, Charles Theillet. Overall design: For miR profiling total RNA were extracted uzing Trizol (Invitrogen/Thermo-Fisher, Illkirch-Graffenstaden, France ) according to manufacturer’s instructions from 18 samples. All samples are in duplicates. samples corresponding to HMEC cell just after cell culture establishement are named R2. Two samples correspond to HMEC samples shortly after shP53 transduction (R2shP53early) and several weeks after shP53 transduction(R2shP53late). HMEC was then transduced with oncogene construct (either HRASV12, WNT1 or CCNE1), samples are called R2shp53-ONCOGENE.Late. Finaly,R2shp53-ONCOGENE samples were grown in soft agar. Samples are named R2shp53-ONCOGENE.SA after selection in soft agar. For exact timing see the associated publication. Less...