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Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas

ABSTRACT: Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas

OTHER RELATED OMICS DATASETS IN: GSE97293

PROVIDER: PRJNA381213 | ENA |

REPOSITORIES: ENA

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Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [expression]

Project description:Transcriptomic profiling of human breast tumors. Genomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 53 invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Array-CGH results was validated by FISH using tumors showing 8p11-p12 DNA amplification and expression profiling was confirmed using qPCR for 11 transcripts. Low-level gain, high-level gain/amplification, heterozygous loss and homozygous deletion (henceforth referred to as gain, amplification, loss and deletion) were defined as log2 ratio thresholds set at +0.2, >= +0.5, -0.2 and <=-1.0, respectively.

2017-03-30 | GSE97177 | GEO

The 8p11-p12 amplicon oncogene ASH2L regulates expression of genes involved in tumorigenic processes via promoter H3K4me3 in luminal breast cancer. (SUM-44 ASH2L knockdown H3K4me3 ChIP-seq)

Project description:Amplification of the 8p11-p12 genomic region occurs in 30% of luminal B breast cancers and results in coordinate overexpression of several oncogenes, including ASH2L, which upregulates gene expression via promoter tri-methylation of lysine 4 on histone 3 (H3K4me3). Since 8p11-p12 amplification is associated with endocrine resistance, the major cause of breast cancer mortality, understanding the underlying biology is essential to improving treatment options for patients. To explore the role of amplified and overexpressed ASH2L on epigenetic regulation of gene expression, we performed H3K4me3 ChIP-seq and RNA-seq in breast cancer cells with ASH2L amplification and overexpression following ASH2L knockdown and assessed the biological effects of the suite of genes identified in this manner. We discovered that ASH2L-regulated genes are implicated in cell cycle processes and response to the CDK4/6 inhibitor palbociclib and confirmed these effects in additional breast cancer cell lines. We also discovered that ASH2L regulates expression of another 8p11-p12 amplicon oncogene NSD3, also an epigenome modifier, which has previously been shown to result in overexpression and estrogen-independent activation of ERα. Together, these data establish ASH2L as a breast cancer oncogene and an important component of the 8p11-p12 amplicon that acts as an oncogenic unit in breast cancer.

2024-05-24 | GSE99669 | GEO

Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-31 | GSE97293 | GEO

Homo sapiens

Project description:Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [expression]

| PRJNA380897 | ENA

Homo sapiens

Project description:Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [aCGH]

| PRJNA381215 | ENA

Homo sapiens

Project description:Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [SNP_genotyping]

| PRJNA392039 | ENA

Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [SNP_genotyping]

Project description:SNP genotyping of human breast tumors

2019-04-17 | GSE100529 | GEO

Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [aCGH]

Project description:DNA copy number alterations play an important role in cancer development and progression by changing the transcriptional levels of key cancer-related genes. However, gene expression patterns may also be affected by other mechanisms. To test these basic principles, we have applied genome-wide screening techniques to 53 invasive breast tumors with array comparative genomic hybridization and gene expression microarrays to assess the direct effect of gene dosage on gene expression levels and independently to test the effect of other mechanisms on transcriptional levels. Low-level gain, high-level gain/amplification, heterozygous loss and homozygous deletion (henceforth referred to as gain, amplification, loss and deletion) were defined as log2 ratio thresholds set at +0.2, ≥+0.5, -0.2 and ≤-1.0, respectively.

2017-03-31 | GSE97292 | GEO

Homo sapiens

Project description:Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [RNA-seq]

| PRJNA393113 | ENA

Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [RNA-seq]

Project description:Transcriptomic profiling of human breast tumors using RNA sequencing

2019-04-17 | GSE100799 | GEO