Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171121 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A collection of genetically engineered mouse models (GEMM) of colorectal cancer (CRC) were created, and primary tumors from these GEMMs were analyzed. Primary CRC tumors from these GEMMs were genotyped to confirm that they contain the core genetic lesions of interest, including APC, P53, KRAS, and BRAF. Primary tumors from GEMMs with combinations of lesions of interest were analyzed by whole genome expression, and their expression profiles were compared to determine how they segregate. Signatures were then generated from GEMM tumors of interest and compared to human clinical datasets with expression and outcome data. Primary tumors from CRC GEMMs with different combinations of mutant alleles of interested were generated and analyzed. Alleles include mutant forms of APC (A), P53 (P), KRAS (K) and BRAF (B).
2014-07-01 | E-GEOD-50794 | biostudies-arrayexpress
Project description:Genetic and epigenetic alterations are essential for the initiation and progression of human cancer. We previously reported that primary human medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation in critical developmental pathways. To determine whether genetically engineered mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In contrast to human samples, very few loci with cancer-specific DNA hypermethylation were detected, and in almost all cases the degree of methylation was relatively modest compared to the dense hypermethylation in the human cancers. To determine if this finding was common to other GEMMs, we examined a Burkitt lymphoma and breast cancer model and did not detect promoter CpG island DNA hypermethylation, suggesting that human cancers and at least some GEMMs are fundamentally different with respect to this epigenetic modification. These findings provide an opportunity to both better understand the mechanism of aberrant DNA methylation in human cancer and construct better GEMMs to serve as preclinical platforms for therapy development. Examination of DNA methylation in one representative human medulloblastoma patient sample and three different mouse models of medulloblastoma using RRBS
2013-10-10 | E-GEOD-45341 | biostudies-arrayexpress
Project description:A collection of genetically engineered mouse models (GEMM) of colorectal cancer (CRC) were created, and primary tumors from these GEMMs were analyzed. Primary CRC tumors from these GEMMs were genotyped to confirm that they contain the core genetic lesions of interest, including APC, P53, KRAS, and BRAF. Primary tumors from GEMMs with combinations of lesions of interest were analyzed by whole genome expression, and their expression profiles were compared to determine how they segregate. Signatures were then generated from GEMM tumors of interest and compared to human clinical datasets with expression and outcome data.
2014-07-01 | GSE50794 | GEO
Project description:CGH analysis of mouse mammary gland tumors from eight genetically-engineered mouse models
| PRJNA303965 | ENA
Project description:Background: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models (GEMMs) are useful resources for studying breast cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and improve preclinical drug validation. Results: Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes (classes). Across species analyses using three independent human breast cancer datasets identified eight murine classes that represent specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWap-Myc, and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathways between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis and candidate pathways for therapeutic intervention. Conclusion: This study consolidates murine models of breast carcinoma into the largest comprehensive transcriptomic dataset to date to identify human-mouse disease subtype counterparts. This approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple GEMMs are needed to represent the diversity of human breast cancers. These trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of the human disease subtypes are used. Keywords: breast cancer, comparative genomics, genetically engineered mouse models, and molecular pathway signatures reference x sample
2013-11-04 | E-GEOD-42640 | biostudies-arrayexpress
Project description:Genetic and epigenetic alterations are essential for the initiation and progression of human cancer. We previously reported that primary human medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation in critical developmental pathways. To determine whether genetically engineered mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In contrast to human samples, very few loci with cancer-specific DNA hypermethylation were detected, and in almost all cases the degree of methylation was relatively modest compared to the dense hypermethylation in the human cancers. To determine if this finding was common to other GEMMs, we examined a Burkitt lymphoma and breast cancer model and did not detect promoter CpG island DNA hypermethylation, suggesting that human cancers and at least some GEMMs are fundamentally different with respect to this epigenetic modification. These findings provide an opportunity to both better understand the mechanism of aberrant DNA methylation in human cancer and construct better GEMMs to serve as preclinical platforms for therapy development. Genome-wide DNA methylation profiles generated using the Denaturation Analysis of Methylation Differences (DAMD) assay of cancer versus normal samples.
2013-10-10 | E-GEOD-45240 | biostudies-arrayexpress
Project description:Anti-cancer drug testing is challenging, but genetically engineered mouse models (GEMMs) and orthotopic, syngeneic transplants (OSTs) may offer advantages for pre-clinical testing including an intact microenvironment. We examined the efficacy of six chemotherapeutic or targeted anti-cancer drugs, alone and in combination, using over 500 GEMMs/OSTs representing three distinct breast cancer subtypes: Basal-like (C3(1)-T-antigen GEMM), Luminal B (MMTV-Neu GEMM), and Claudin-low (T11/TP53-/- OST). While a few single agents offered exceptional efficacy like lapatinib in the Neu/ERBB2 driven model, combination therapies tended to be more active and life prolonging. Using expression profiling of chemotherapy treated murine tumors, we identified an expression signature that was able to predict pathological complete response to neoadjuvant anthracycline-taxane treated human breast cancer patients, even after accounting for the common clinical variables and other genomic signatures. These results show that credentialed murine models can predict the efficacy of would-be anti-cancer compounds in humans, and that GEMMs can be used to develop new biomarkers of therapeutic responsiveness in humans. control X treatment
2014-01-01 | E-GEOD-37915 | biostudies-arrayexpress
Project description:Transcriptomic Classification of Genetically Engineered Mouse Models of Breast Carcinoma Identifies Human Subtype Counterparts
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Project description:Mutational landscape in genetically engineered, carcinogen-induced, and radiation-associated mouse models of sarcoma
| PRJNA516973 | ENA
Project description:Expression data from synovial sarcoma-like tumors induced in a genetically engineered mouse model
| PRJNA111471 | ENA