Project description:Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle and is an aggressive soft tissue tumor, have complex genetic abnormalities and could be defined as three molecular subtypes. Since that the molecular heterogeneity of LMS, the pathogenesis analysis per subtype will be highly necessary and helpful to understand the etiology of this more common sarcoma. Within this study, we collected four Myometrium, three Leiomyoma, three LMS cell lines and 99 LMSs (GSE45510), performed the system-wide gene expression profiling by 3'end RNA Sequencing, and found that there are significant different molecular pathways along the pathogenesis for those three molecular subtypes.
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle and is an aggressive soft tissue tumor, have complex genetic abnormalities and could be defined as three molecular subtypes. Since that the molecular heterogeneity of LMS, the pathogenesis analysis per subtype will be highly necessary and helpful to understand the etiology of this more common sarcoma.
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation, and there are three molecular subtypes of LMS which have been defined previously by our lab. To further validate these subtypes and identify potential therapeutic targets in each subtype, we profiled the LMS cases from each subtype with RNA-Seq technology.
Project description:The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS, fibroids, and normal myometrium (NL) to identify clinically relevant molecular subtypes. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods.
Project description:The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS, fibroids, and normal myometrium (NL) to identify clinically relevant molecular subtypes. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. RNA was extracted from frozen tissues and hybridized to microarrays. Unsupervised and supervised analyses were performed using standard methods.
Project description: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.