Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA139235 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumors acquire somatic DNA copy number aberrations, leading to activation of oncogenes and inactivation of tumor suppressors. Many studies have focused on the analysis of single copy number aberrations and associated driver genes, but few studies have performed combinatorial analyses. We propose a genome-wide scoring framework to find mutually exclusive gains and losses. Mutually exclusive copy number aberrations can identify genes whose oncogenic function is redundant, either by functioning in the same pathway or in a parallel pathway. As one gene is aberrated the selective pressure for its partner is alleviated which leads to a mutually exclusive perturbation pattern. In a dataset of mouse models for invasive lobular carcinoma we found three mutually exclusive DNA amplifications, containing several well-known oncogenes: the Met proto-oncogene on chromosome 6, the cluster of Birc2, Birc3 and Yap1 genes on chromosome 9, and Nras on chromosome 3. Furthermore, gene expression or protein expression of these genes correlates very well with copy number data indicating that they are the target of the amplification. Although homologous amplifications in human tumors are rare, the mutual exclusivity of MET, BIRC/YAP1 and NRAS is maintained in a variety of cancer types. This suggests a novel function for YAP1 in the mitogen-activated signaling pathway by association with MET and NRAS, known players in this pathway. This function is independent to the propensity of YAP1 to cause Epithelial-to-Mesenchymal transition. aCGH data of 67 mouse mammary tumors from K14-Cre and WAP-Cre driven P53-F/F;Cdh1-F/F animals - tumor DNA hybridized against same-animal splenic DNA
2011-12-01 | E-GEOD-28432 | biostudies-arrayexpress
Project description:Tumors acquire somatic DNA copy number aberrations, leading to activation of oncogenes and inactivation of tumor suppressors. Many studies have focused on the analysis of single copy number aberrations and associated driver genes, but few studies have performed combinatorial analyses. We propose a genome-wide scoring framework to find mutually exclusive gains and losses. Mutually exclusive copy number aberrations can identify genes whose oncogenic function is redundant, either by functioning in the same pathway or in a parallel pathway. As one gene is aberrated the selective pressure for its partner is alleviated which leads to a mutually exclusive perturbation pattern. In a dataset of mouse models for invasive lobular carcinoma we found three mutually exclusive DNA amplifications, containing several well-known oncogenes: the Met proto-oncogene on chromosome 6, the cluster of Birc2, Birc3 and Yap1 genes on chromosome 9, and Nras on chromosome 3. Furthermore, gene expression or protein expression of these genes correlates very well with copy number data indicating that they are the target of the amplification. Although homologous amplifications in human tumors are rare, the mutual exclusivity of MET, BIRC/YAP1 and NRAS is maintained in a variety of cancer types. This suggests a novel function for YAP1 in the mitogen-activated signaling pathway by association with MET and NRAS, known players in this pathway. This function is independent to the propensity of YAP1 to cause Epithelial-to-Mesenchymal transition.
2011-12-01 | GSE28432 | GEO
Project description:miRNA profiling of normal and tumorigenic mouse mammary tissue. Mouse genotypes consist of wildtype, MMTV-Met, MMTV-Met;Trp53fl/+;Cre, and Trp53fl/+;Cre. One-color design. Samples consist of 2 normal tissues, 7 MMTV-Met tumors, 8 MMTV-Met;Trp53fl/+;Cre tumors, and 8 Trp53;Cre tumors.
2013-03-04 | E-GEOD-41723 | biostudies-arrayexpress
Project description:Transcriptional profiling of normal and tumorigenic mouse mammary tissue. Mouse genotypes consist of wildtype, MMTV-Met, MMTV-Met;Trp53fl/+;Cre, and Trp53fl/+;Cre. Two-color common reference design. Samples consist of 11 normal tissues, 8 MMTV-Met tumors, 14 MMTV-Met;Trp53fl/+;Cre tumors, and 8 Trp53;Cre tumors.
2013-03-04 | E-GEOD-41601 | biostudies-arrayexpress
Project description:Transcriptional profiling of normal and tumorigenic mouse mammary tissue. Mouse genotypes consist of wildtype, MMTV-Met, MMTV-Met;Trp53fl/+;Cre, and Trp53fl/+;Cre. Two-color common reference design. Samples consist of 4 normal tissues, 8 MMTV-Met tumors, 10 MMTV-Met;Trp53fl/+;Cre tumors, and 8 Trp53;Cre tumors.
2013-03-04 | E-GEOD-41632 | biostudies-arrayexpress
Project description:cMET is a well known oncogene whose activation is widely implicated in tumorigenesis and metastasis. To investigate the effects of acute inhibitoin of cMET signaling in the mammary tumors, we inhibited cMET activation in xenograft mammary tumors that were derived from a MET amplified mouse mammary tumor cell line and analyzed the transcriptional alteration between vehicle and MET inhibitor treated tumors.
2020-02-23 | GSE52097 | GEO
Project description:Here we present a novel example of genetic heterogeneity in human malignant brain tumors, in which multiple closely-related driver genes are amplified and activated simultaneously in adjacent intermingled cells. We have observed up to 3 different receptor tyrosine kinases (EGFR, MET, PDGFRA) amplified in single tumors in different cells in a mutually exclusive fashion. However, these subpopulations cannot be always observed with a genome wide studies such as aCGH. Here we include aCGH on three such mosaic cases. Analyses were performed on 350 archival specimens of glioblastoma, WHO Grade IV, seen at the Department of Pathology, Massachusetts General Hospital from 2009 to 2011. CGH on three such mosaic cases.
2012-01-01 | E-GEOD-33483 | biostudies-arrayexpress
Project description:Gain-of-function mutation of PIK3CA represents one of the most common oncogenic events in human malignancy, making PI3K an attractive target for cancer therapy. Despite the great promise of targeted therapy, drug resistance is likely to develop, causing treatment failure. To elucidate resistance mechanisms to PI3K-targeted therapy, we constructed a mouse model of breast cancer conditionally expressing PIK3CA-H1047R. Surprisingly, the majority of mammary tumors induced by PIK3CA-H1047R expression recurred following PIK3CA-H1047R inactivation. Genomic analyses of recurrent tumors revealed multiple lesions, including spontaneous focal amplification of c-Met or c-Myc. While amplification of c-Met allowed tumor survival dependent on activation of endogenous PI3K, tumors with amplification of c-Myc become independent of the PI3K pathway. Functional analyses further demonstrated that c-Myc contributed to tumors’ independence of oncogene and resistance to PI3K inhibition. Together, our data suggest that MYC elevation in tumors may be a potential mechanism conferring resistance to current PI3K-targeted therapies. Affymetrix SNP array analysis was performed with Mouse Diversity Genotyping Arrays (Affymetrix) on genomic DNA extracted from frozen biopsies of 6 recurrent mouse mammary tumor samples. Copy number analysis was performed for the mouse mammary tumors using genomic DNA from normal mammary tissue as the reference for copy number inference.
2011-08-01 | E-GEOD-27691 | biostudies-arrayexpress
Project description:Eighteen independent neurospheres derived from patients affected by primary glioblastoma were grouped into “classical”, “mesenchymal” or “proneural” subtypes according to analysis of genetic lesions and gene expression profiling. Here we show that expression of the MET oncogene, encoding the tyrosine kinase receptor for HGF, associates with mesenchymal and proneural neurospheres (Met-pos-NS). Met expression is almost absent from classical neurospheres (Met-neg-NS), and mutually exclusive with amplification and expression of the EGF receptor gene. Met-pos-NS and Met-neg-NS display distinct growth factor requirements, differentiate along divergent pathways, and generate tumors with distinctive histological features. Met-pos-NS contain a variable percentage of Met positive (Methigh) and Met negative (Metneg) cells. After purification, only Methigh cells display clonogenic ability in vitro, and regenerate neurospheres containing both Methigh and Metneg cells. After in vivo transplantation, Methigh cells display highly enriched tumorigenic potential as compared with Metneg cells. At functional level, in Methigh cells, HGF concomitantly sustains proliferation, clonogenicity, expression of self-renewal markers, migration and invasion. These data show that Met is a functional marker of glioblastoma stem cells, and a candidate target for molecular diagnosis and therapy of a glioblastoma subset. 37 samples (17 replicate samples and 1 triplicate sample)
2012-10-05 | E-GEOD-36426 | biostudies-arrayexpress