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Homo sapiens

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

OTHER RELATED OMICS DATASETS IN: GSE97293

PROVIDER: PRJNA381215 | ENA |

REPOSITORIES: ENA

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

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

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

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

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

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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.

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Project description:A multi-omics approach to decipher the complexity of drug resistance in diffuse large B-cell lymphoma

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Project description:Genomic complexity in breast tumors has been associated with aggressive disease and less favorable outcome. Recently, we developed an algorithm to calculate complexity scores per chromosome arm in order to sub-classify breast tumors with respect to progression paths and prognosis. We have further developed this method to calculate probe-focused complexity scores per sample, enabling identification of regions with recurrent complexities and grouping of tumors according to genome-wide complexity patterns. Probe-focused complexity scores were calculated based on data derived from aCGH analyses of 394 invasive ductal breast carcinomas. These continuous complexity scores (CCI) were used to identify regions with recurrent high level complexity, and the regional complexity scores were correlated to clinicopathological variables and survival data. A total of 25 recurrent regions with high level complexity were identified. Regional complexities on chromosome arms 8p, 11q and 17q were each associated with clinical parameters associated with aggressive disease. Complexity patterns were different between tumors of different gene expression subtypes. Multivariate Cox analysis revealed that regional complexity on 17q21.32-q21.33 was significantly associated with shorter survival, independent of established clinical variables.

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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.

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Project description:Transforming properties of 8p11-12 amplified genes in human breast cancer

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