Identification of conserved gene expression features across human and murine mammary tumors
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE3165
PROVIDER: PRJNA93005 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mice have been used as models for human breast cancers for many years, however, it is still unclear which murine models faithfully represent human tumor phenotypes. To address this question, we used DNA microarrays to characterize 10 different murine mammary models and compared these data to the expression patterns from primary human breast tumors. Hierarchical clustering analysis of the murine samples showed that the WAP-Myc, MMTV-Neu, MMTV-PyMT, WAP-Int3, and C3(1)-Tag tumors were highly correlated within each model. Other models, including the WAP-T_121 , MMTV-Wnt1, and DMBA-induced tumor model, did not show this consistency and gave rise to tumors with potentially different cell types of origin. A combined clustering analysis of the murine tumors with 102 human breast tumors showed many shared expression features. These features included a proliferation signature, an Interferon-regulated pattern, and patterns reflective of the presence of lymphocytes and fibroblasts. Murine tumors could be categorized according to their presumed cellular origins; the C3(1)-Tag, BRCA1+/-; p53+/-;IR, and DMBA-treated models displayed expression characteristics of human basal-like breast tumors; the MMTV-Neu, MMTV-PyMT, and WAP-Myc models shared features with human luminal breast tumors including the high expression of GATA3 and XBP1. In some cases, single mouse models did not reproduce the entire expression pattern seen in a specific human subtype; rather portions of a subtype’s expression profile were captured/represented by different murine models. The presence of shared patterns of expression between mice and humans provides a common framework for the direct comparison and integration of animal models with human breast Keywords: reference x sample
2007-05-01 | GSE3165 | GEO
Project description:Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors.Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.
| S-EPMC1929138 | biostudies-literature
Project description:Breast cancer is the second leading cause of cancer related death in American women. Patient care is complicated by inherent tumor heterogeneity that can be classified into at least six intrinsic subtypes. While targeted treatments are standard of care for most subtypes, there remains a clinical need for targeted therapies against basal-like tumors that are typically ‘triple negative breast cancers’. As such, the molecular mechanisms underlying basal-like tumors are under intense investigation to identify genetic drivers and possible drug targets of this subtype. Somatic p53 mutations are one of the most common genetic events in basal-like breast tumors. This genetic foundation primes cells to accumulate secondary genetic aberrations, a subset of which is predicted to promote tumorigenesis. To identify additional drivers of basal-like tumors, a comparative study between human and murine tumors was performed utilizing a p53null mammary transplant murine model. The p53null mammary transplant murine model produced a genomically diverse set of tumors, a subset of which we show resemble the human basal-like subtype. Microarray and sequencing technologies were used to interrogate the secondary genetic aberrations of these murine tumors which were then compared to human basal-like tumors to highlight conserved features. Of the ‘omic’ datasets analyzed, DNA copy number variation produced the largest number of conserved candidate driver genes. These candidate gene lists were further filtered using a DNA-RNA Pearson correlation cutoff of 0.5 and a requirement that the gene was deemed essential in at least one human basal-like cell line from a genome-wide RNA-mediated interference screen database. These steps highlighted seven potential driver genes that are at amplified loci in both murine and human basal-like tumors: Atp11a, Col4a2, Cul4a, Lamp1, Met, Pnpla6, and Tubgcp3. Inhibition of Met using Crizotinib caused Met amplified tumors to regress, confirming that this genetic event is a driver in a subset of p53null transplant mammary tumors. This study identifies MET as a driver of basal-like murine tumors, thus identifying a shared potential driver of human basal-like breast cancer. Our results also highlight the importance of comparative genomic studies for discovering drug targets and for providing models to study whether patient populations are likely to respond to selective targeted treatments.
2016-07-08 | GSE71071 | GEO
Project description:ATF3-induced mammary tumors exhibit molecular features of human basal-like breast cancer
| PRJNA683050 | ENA
Project description:Transcriptional profiling of mammary tumors that occurs in parous, BK5.ATF3 mice, compared to adjacent normal mammary tissue
2021-03-23 | GSE162804 | GEO
Project description:<p>The identification of efficient and sensitive biomarkers for non-invasive tests is one of the major challenges in cancer diagnosis. To address this challenge, metabolomics is widely applied for identifying biomarkers that detects abnormal changes in cancer patients. Canine mammary tumors exhibit physiological characteristics identical to those in human breast cancer and serve as a useful animal model to conduct breast cancer research. Here, we aimed to provide a reliable large-scale metabolite dataset collected from dogs with mammary tumors, using proton nuclear magnetic resonance spectroscopy. We identified 55 metabolites in urine samples from 20 benign, 87 malignant, and 49 healthy control subjects. This dataset provides details of mammary tumor-specific metabolites in dogs and insights into cancer-specific metabolic alterations that share similar molecular characteristics.</p>
2022-02-24 | MTBLS2550 | MetaboLights
Project description:Using microarray technology, we aim to identify genes affecting the biology of mammary tumor cancers in dogs. Canine mammary gland tumors (CMGTs) are the most common neoplasms in sexually intact female dogs. CMGTs have been suggested as a model for studying human breast cancer because of several similarities, including the relative age of onset, risk factors, incidence, histological and molecular features, biological behavior, metastatic pattern, and responses to therapy.
2018-12-26 | GSE104733 | GEO
Project description:Molecular profiling was used to classify mammary tumors that develop in MTB-IGFIR transgenic mice. It was determined that the primary mammary tumors (PMT), which develop due to elevated expression of the type I insulin-like growth factor receptor (IGF-IR) in mammary epithelial cells, most closely resemble murine tumors with basal-like or mixed gene expression profiles and with human basal-like breast cancers. Downregulation of IGF-IR transgene in MTB-IGFIR tumor-bearing mice leads to the regression of most of the tumors followed by tumor re-appearance in some of the mice. These tumors that re-appear following IGF-IR transgene downregulation do not express the IGF-IR transgene and cluster with murine mammary tumors that express a mesenchymal gene expression profile and with human claudin-low breast cancers. Therefore, IGF-IR overexpression in murine mammary epithelial cells induces mammary tumors with primarily basal-like characteristics while tumors that develop following IGF-IR downregulation express a gene signature that most closely resembles human claudin-low breast tumors.
2011-10-01 | GSE32152 | GEO
Project description:The retinoblastoma tumor suppressor, Rb, is implicated in luminal-B and basal-like breast carcinomas, yet its effect on mammary gland development and causal role in breast cancer subtypes remain undefined. Here we show that conditional deletion of Rb in mouse mammary epithelium led to expansion of the stem/progenitor cells and to focal acinar hyperplasia with squamous metaplasia. These uniform lesions progressed into histologically diverse, transplantable mammary adenocarcinomas and adenosquamous carcinomas with features of luminal-B or basal-like carcinomas. A subset of basal-like but none of the luminal-B tumors expressed mutant p53. These results demonstrate a causative role for Rb in the etiology of breast cancer subtypes and implicate p53 status as a determinant of tumor phenotype after Rb loss. Keywords: reference x sample Will be updated soon
2010-07-06 | E-GEOD-14457 | biostudies-arrayexpress
Project description:Mouse mammary tumors and uminal cells
| PRJNA625196 | ENA