Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genetic Heterogeneity in Mouse Mammary Tumors

ABSTRACT: Human cancers result from a complex series of genetic alterations resulting in heterogeneous disease states. Dissecting this heterogeneity is critical for understanding underlying mechanisms and providing opportunities for therapeutics matching the complexity. Mouse models of cancer have generally been employed to reduce this complexity and focus on the role of single genes. Nevertheless, our analysis of tumors arising in the MMTV-Myc model of mammary carcinogenesis reveals substantial heterogeneity, seen in both histological and expression phenotypes. One contribution to this heterogeneity is the substantial frequency of activating Ras mutations, the frequency of which can be changed by alterations in Myc. Additionally, we show that these Myc-induced mammary tumors exhibit even greater heterogeneity, revealed by distinct histological subtypes as well as distinct patterns of gene expression, than many other mouse models of tumorigenesis. Two of the major histological subtypes are characterized by differential patterns of cellular signaling pathways, including B-Catenin and Stat3 activities. We also demonstrate the predictive nature of this approach though examining metastatic potential. Together, these data reveal that a combination of histological and genomic analyses can uncover substantial heterogeneity in mammary tumor formation and therefore highlight aspects of tumor phenotype not evident in the population as a whole. Keywords: Transcription factor expression analysis

ORGANISM(S): Mus musculus

PROVIDER: GSE15904 | GEO | 2009/08/28

SECONDARY ACCESSION(S): PRJNA116895

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genetic Heterogeneity in Mouse Mammary Tumors

Project description:Human cancers result from a complex series of genetic alterations resulting in heterogeneous disease states. Dissecting this heterogeneity is critical for understanding underlying mechanisms and providing opportunities for therapeutics matching the complexity. Mouse models of cancer have generally been employed to reduce this complexity and focus on the role of single genes. Nevertheless, our analysis of tumors arising in the MMTV-Myc model of mammary carcinogenesis reveals substantial heterogeneity, seen in both histological and expression phenotypes. One contribution to this heterogeneity is the substantial frequency of activating Ras mutations, the frequency of which can be changed by alterations in Myc. Additionally, we show that these Myc-induced mammary tumors exhibit even greater heterogeneity, revealed by distinct histological subtypes as well as distinct patterns of gene expression, than many other mouse models of tumorigenesis. Two of the major histological subtypes are characterized by differential patterns of cellular signaling pathways, including B-Catenin and Stat3 activities. We also demonstrate the predictive nature of this approach though examining metastatic potential. Together, these data reveal that a combination of histological and genomic analyses can uncover substantial heterogeneity in mammary tumor formation and therefore highlight aspects of tumor phenotype not evident in the population as a whole. Keywords: Transcription factor expression analysis 20 MMTV-Neu Tumors, 25 Papillary MMTV-Myc T58A and 81 MMTV-Myc tumors of various histological subtypes were arrayed.

2010-03-03 | E-GEOD-15904 | biostudies-arrayexpress

Gene expression differences of mammary tumors after treatment

Project description:Current therapeutic outcomes for breast cancer underscore the complexity of treating a heterogeneous disease. Indeed, studies have shown that differences in gene expression among patients with the same subtype of breast cancer are correlated with the response to treatment. This strongly suggests that there is an urgent need to treat breast cancer with a personalized approach. Here we employed cell signaling pathway signatures predict pathway activity in subtypes of MMTV-Myc mammary tumors. We then split tumors into subsets and developed individualized combinatorial treatments for two subtypes with distinct pathway activation patterns. In this treatment, we focus on papillary subtype-specific treatment, targeting Myc, Stat3, and Akt pathways. We compared gene expression differences after treatment.

2018-05-09 | GSE81284 | GEO

MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer

Project description:Triple-negative breast cancer (TNBC) patients have a poor prognosis and few treatment options. Mouse models of TNBC are important for development of new therapies, however, few mouse models represent the complexity of TNBC. Here, we develop a female TNBC murine model by mimicking two common TNBC mutations with high co-occurrence: amplification of the oncogene MYC and deletion of the tumor suppressor PTEN. This Myc;Ptenfl model develops heterogeneous triple-negative mammary tumors that display histological and molecular features commonly found in human TNBC. Our research involves deep molecular and spatial analyses on Myc;Ptenfl tumors including bulk and single-cell RNA-sequencing, and multiplex tissue-imaging. Through comparison with human TNBC, we demonstrate that this genetic mouse model develops mammary tumors with differential survival and therapeutic responses that closely resemble the inter- and intra-tumoral and microenvironmental heterogeneity of human TNBC, providing a pre-clinical tool for assessing the spectrum of patient TNBC biology and drug response.

2022-10-17 | GSE215071 | GEO

MYC Deregulation and PTEN Loss Model Tumor and Stromal Heterogeneity of Aggressive Triple-Negative Breast Cancer

2023-07-18 | GSE215070 | GEO

HumanCore SNP data for an Integrated genomic analysis of oligodendroglial tumours identifies subgroups of 1p/19q co-deleted oligodendrogliomas

Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net: Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished based on the IDH mutation and the 1p/19q co-deletion. Here we performed an integrated analysis of the transcriptome, genome and methylome of 156 OT. Beyond the 3 well-known molecular classes, our multi-omics classification revealed 3 subgroups within 1p/19q co-deleted tumours, associated with different expression patterns of oligodendroglial progenitor cell (OPC), astrocytic, oligodendrocytic and neuronal lineage genes. The validity of these 3 subgroups was confirmed on public datasets. The OPC-like group was associated with a more aggressive histological and genomic profile and with MYC activation that occurred through various alterations including MYC locus genomic gain, MYC exon 3 hypo-methylation and down-regulation of microRNA-34b/c. In the lower grade glioma TCGA dataset, the OPC-like group was associated with a poorer outcome independently from histological grade. Our study unravels previously unrecognized heterogeneity among 1p/19q co-deleted tumours.

2016-03-11 | E-MTAB-3896 | biostudies-arrayexpress

Expression data as part of an Integrated analysis of oligodendroglial tumours

2016-03-11 | E-MTAB-3892 | biostudies-arrayexpress

Methylation data as part of an Integrated analysis of oligodendroglial tumours

2016-03-11 | E-MTAB-3903 | biostudies-arrayexpress

miRNA data for an Integrated genomic analysis of oligodendroglial tumours identifies subgroups of 1p/19q co-deleted oligodendrogliomas

2016-03-11 | E-MTAB-3901 | biostudies-arrayexpress

HumanOmniExpress SNP data for an Integrated genomic analysis of oligodendroglial tumours identifies subgroups of 1p/19q co-deleted oligodendrogliomas

Project description:'A Cartes d''Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net: Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished based on the IDH mutation and the 1p/19q co-deletion. Here we performed an integrated analysis of the transcriptome, genome and methylome of 156 OT. Beyond the 3 well-known molecular classes, our multi-omics classification revealed 3 subgroups within 1p/19q co-deleted tumours, associated with different expression patterns of oligodendroglial progenitor cell (OPC), astrocytic, oligodendrocytic and neuronal lineage genes. The validity of these 3 subgroups was confirmed on public datasets. The OPC-like group was associated with a more aggressive histological and genomic profile and with MYC activation that occurred through various alterations including MYC locus genomic gain, MYC exon 3 hypo-methylation and down-regulation of microRNA-34b/c. In the lower grade glioma TCGA dataset, the OPC-like group was associated with a poorer outcome independently from histological grade. Our study unravels previously unrecognized heterogeneity among 1p/19q co-deleted tumours.'

2016-06-15 | E-MTAB-3902 | biostudies-arrayexpress

HumanCNV-370 data for an Integrated genomic analysis of oligodendroglial tumours identifies subgroups of 1p/19q co-deleted oligodendrogliomas

2016-03-11 | E-MTAB-3907 | biostudies-arrayexpress