Gene expression profiling of breast fibroadenomas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE55594 | GEO | 2014/06/13
SECONDARY ACCESSION(S): PRJNA240194
REPOSITORIES: GEO
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Project description:Fibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. Here, we show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes. Microarray gene expression profiling was performed on 10 breast fibroadenomas and a combination of unsupervised and supervised clustering was performed to determine any differentially activated pathways between samples with mutated and non-mutated MED12.
2014-06-13 | E-GEOD-55594 | biostudies-arrayexpress
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2016-03-03 | E-GEOD-70653 | biostudies-arrayexpress
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2016-03-03 | GSE70653 | GEO
Project description:Uterine fibroids (UFs) are benign tumours affecting up to 80% of women of reproductive age. Although mutations in MED12 or HMGA2 account for the majority of UF occurrence, the processes by which these lead to UFs remain poorly understood. Here we present a comprehensive systems biology study, merging clinical, genetic, transcriptomic and proteomic information to better understand the patho-mechanisms underlying UF.
2022-05-01 | GSE199849 | GEO
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2018-12-21 | GSE95613 | GEO
Project description:Genetic heterogeneity can provide tumors with opportunities for therapy evasion, however the degree of genetic heterogeneity within metastatic melanomas has not been thoroughly investigated. We therefore isolated DNA from different regions of formalin fixed paraffin embedded metastatic melanoma tissue samples and subjected them to amplicon sequencing-based profiling of mutations in a panel of well known cancer genes using the Ion Ampliseq Cancer Panel.
2013-09-08 | E-MTAB-1794 | biostudies-arrayexpress
Project description:Meningiomas are mostly benign brain tumors, with a potential for becoming atypical or malignant. Based on comprehensive genomic, transcriptomic and epigenomic analyses of meningiomas, we compared benign tumors to atypical ones. We show that the vast majority of primary (de novo atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent mutations in SMARCB1. These tumors harbor increased H3K27me3 repressive signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2 binding sites in human embryonic stem cells (hESCs, thereby phenocopying a more primitive cellular state. Consistent with this observation, and based on differential gene expression analysis as well as correlation of mRNA:miRNA regulatory networks, atypical meningiomas exhibit up-regulation of EZH2, the catalytic subunit of the PRC2 complex, well as the E2F2 and FOXM1 transcriptional networks that promote proliferation through activation of the cell cycle pathways. In addition, based on H3K27ac ChIP-seq analysis, we show atypical tumors to display an activated super-enhancer near the meningeal identity transcription factor ZIC1, leading to its transcriptional upregulation. Importantly, these primary atypical meningiomas do not harbor activating TERT promoter mutations, which have been reported in atypical tumors that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas, differentiating their profile from benign and progressed tumors and establishing novel therapeutic targets.
2017-01-12 | GSE93519 | GEO
Project description:Meningiomas are mostly benign brain tumors, with a potential for becoming atypical or malignant. Based on comprehensive genomic, transcriptomic and epigenomic analyses of meningiomas, we compared benign tumors to atypical ones. We show that the vast majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent mutations in SMARCB1. These tumors harbor increased H3K27me3 repressive signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells (hESCs), thereby phenocopying a more primitive cellular state. Consistent with this observation, and based on differential gene expression analysis as well as correlation of mRNA:miRNA regulatory networks, atypical meningiomas exhibit up-regulation of EZH2, the catalytic subunit of the PRC2 complex, well as the E2F2 and FOXM1 transcriptional networks that promote proliferation through activation of the cell cycle pathways. In addition, based on H3K27ac ChIP-seq analysis, we show atypical tumors to display an activated super-enhancer near the meningeal identity transcription factor ZIC1, leading to its transcriptional upregulation. Importantly, these primary atypical meningiomas do not harbor activating TERT promoter mutations, which have been reported in atypical tumors that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas, differentiating their profile from benign and progressed tumors and establishing novel therapeutic targets.
2016-12-20 | GSE91375 | GEO
Project description:Meningiomas are mostly benign brain tumors, with a potential for becoming atypical or malignant. Based on comprehensive genomic, transcriptomic and epigenomic analyses of meningiomas, we compared benign tumors to atypical ones. We show that the vast majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent mutations in SMARCB1. These tumors harbor increased H3K27me3 repressive signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells (hESCs), thereby phenocopying a more primitive cellular state. Consistent with this observation, and based on differential gene expression analysis as well as correlation of mRNA:miRNA regulatory networks, atypical meningiomas exhibit up-regulation of EZH2, the catalytic subunit of the PRC2 complex, well as the E2F2 and FOXM1 transcriptional networks that promote proliferation through activation of the cell cycle pathways. In addition, based on H3K27ac ChIP-seq analysis, we show atypical tumors to display an activated super-enhancer near the meningeal identity transcription factor ZIC1, leading to its transcriptional upregulation. Importantly, these primary atypical meningiomas do not harbor activating TERT promoter mutations, which have been reported in atypical tumors that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas, differentiating their profile from benign and progressed tumors and establishing novel therapeutic targets.
2016-12-20 | GSE92558 | GEO
Project description:The RNA polymerase II transcriptional Mediator subunit MED12 is broadly implicated in vertebrate brain development, and genetic variation in human MED12 is associated with X-linked intellectual disability and neuropsychiatric disorders. Although prior studies have begun to elaborate the functional contribution of MED12 within key neurodevelopmental pathways, a more complete description of MED12 function in the developing nervous system, including the specific biological networks and cellular processes under its regulatory influence, remains to be established. Herein, we sought to clarify the global contribution of MED12 to neural stem cell (NSC) biology through unbiased transcriptome profiling of mouse embryonic stem (ES) cell-derived NSCs following RNAi-mediated MED12 depletion. A total of 240 genes (177 up, 73 down) were differentially expressed in MED12-knockdown versus control mouse NS-5 (mNS-5) NSCs. Gene set enrichment analysis revealed MED12 to be prominently linked with “cell-to-cell interaction” and “cell cycle” networks, and subsequent functional studies confirmed these associations. Targeted depletion of MED12 led to enhanced NSC adhesion and upregulation of cell adhesion genes, including Syndecan 2 (SDC2). Concomitant depletion of both SDC2 and MED12 reversed enhanced cell adhesion triggered by MED12 knockdown alone, confirming that MED12 negatively regulates NSC cell adhesion by suppressing the expression of cell adhesion molecules. MED12-mediated suppression of NSC adhesion is a dynamically regulated process in vitro, enforced in self-renewing NSCs and alleviated during the course of neuronal differentiation. Accordingly, MED12 depletion enhanced adhesion and prolonged survival of mNS-5 NSCs induced to differentiate on gelatin, effects that were bypassed completely by growth on laminin. On the other hand, MED12 depletion in mNS-5 NSCs led to reduced expression of G1/S phase cell cycle regulators and a concordant G1/S phase cell cycle block without evidence of apoptosis, resulting in a severe proliferation defect. These findings suggest that MED12 contributes to the maintenance of NSC identity through a functionally bipartite role in suppression and activation of gene expression programs dedicated to cell adhesion and G1/S phase cell cycle progression, respectively. MED12 may thus contribute to the regulatory apparatus that controls the balance between NSC self-renewal and differentiation, with important implications for MED12-linked neurodevelopmental disorders.
2016-05-19 | GSE80624 | GEO