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Clonal evolution in multiple myeloma after treatment pressure: heterogenous genomic aberrations and transcriptomic convergence

ABSTRACT: Clonal evolution in multiple myeloma after treatment pressure: heterogenous genomic aberrations and transcriptomic convergence

PROVIDER: PRJNA745931 | ENA |

REPOSITORIES: ENA

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Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence.

Project description: Not available

| S-EPMC9252918 | biostudies-literature

Clonal evolution in multiple myeloma after treatment pressure: heterogenous genomic aberrations and transcriptomic convergence

Project description:Multiple myeloma (MM) is still an incurable plasma cell malignancy that generally responds well to treatment intitially, but eventually becomes refractory. In the present study, genomic and transcriptomic changes were investigated in paired early and late tumor samples of MM patients .

2022-05-01 | GSE179929 | GEO

Glioma escape signature and clonal development under immune pressure [microarray]

Project description:Immunotherapeutic strategies are increasingly important in neuro-oncology and the elucidation of escape mechanisms which lead to treatment resistance is crucial. We investigated the impact of immune pressure on the clonal dynamics and immune escape signature by comparing glioma growth in immunocompetent versus immunodeficient mice. Glioma-bearing wildtype and PD-1-/- mice survived significantly longer than immunodeficient Pfp/Rag2-/- mice. While tumors in Pfp/Rag2-/- mice were highly polyclonal, immunoedited tumors in WT and PD-1-/- mice displayed reduced clonality with emergence of immune escape clones. Tumor cells in wildtype mice were distinguished by an interferon-gamma-mediated response signature with upregulation of genes involved in immunosuppression. Tumor-infiltrating stromal cells, which include macrophages/microglia, contributed even stronger to the immunosuppressive signature than the actual tumor cells. The identified murine immune escape signature was reflected in human patients and correlated with poor survival. In conclusion, cancer immune pressure profoundly shapes the clonal composition and gene regulation in malignant gliomas.

2020-08-31 | GSE151283 | GEO

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations

Project description:Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo. Agilent whole human genome aCGH oligonucleotide microarrays were used to assess copy number aberrations in 79 specimens from 20 patients as well as two pairs of cancer-associated fibroblasts (CAF) and benign/normal associated fibroblasts (NAF). 3 CAF/NAF sample pairs were also assessed for DNA copy number aberrations and copy-neutral LOH using the Infinium HumanOmniExpressExome BeadChip Kit.

2016-02-12 | E-GEOD-76456 | biostudies-arrayexpress

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Project description:Normal Pressure Hydrocephalus

| PRJNA679984 | ENA

Normal Pressure Hydrocephalus

Project description:Normal Pressure Hydrocephalus

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Glioma escape signature and clonal development under immune pressure [RNA-Seq]

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Glioma escape signature and clonal development under immune pressure

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