Single-cell RNA-seq reveals RAD51AP1 as a potent mediator of EGFRvIII in human glioblastomas.

Single-cell RNA-seq reveals RAD51AP1 as a potent mediator of EGFRvIII in human glioblastomas. Aging (Albany NY). 2019 Sep 18;11: Authors: Wang Q, Tan Y, Fang C, Zhou J, Wang Y, Zhao K, Jin W, Wu Y, Liu X, Liu X, Kang C Abstract Recent advances in single-cell RNA sequencing (scRNA-seq) have endowed researchers with the ability to detect and analyze the transcriptomes of individual cancer cells. In the present study, 16,128 tumor cells from EGFR wild-type and EGFRvIII mutant cells were profiled by scRNA-seq. Analyses of scRNA-seq data from both U87MG and U87MG-EGFRvIII libraries revealed inherent heterogeneity in gene expression and biological processes. The cells stably expressing EGFRvIII showed enhanced transcriptional activities and a relatively homogeneous pattern, which manifested as less diverse distributions, gene expression levels and functional annotations compared with those of cells expressing the nonmutated version. Moreover, the differentially expressed genes between the U87MG and U87MG-EGFRvIII groups were mainly enriched in DNA replication, DNA repair and angiogenesis. We compared scRNA-seq data with bulk RNA-seq and EGFRvIII xenograft RNA-seq data. RAD51AP1 was shown to be upregulated in all three databases. Further analysis of RAD51AP1 revealed that it is an independent prognostic factor of glioma. Knocking down RAD51AP1 significantly inhibited tumor volume in an intracranial EGFRvIII-positive GBM model and prolonged survival time. Collec...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research

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In this report, we present the case of a 3-year-old girl with glioblastoma who continues to experience an exceptional and durable response (>2 years) to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib. Our patient presented with persistent and progressive seizure activity that upon workup was the result of a large heterogeneously enhancing, mixed cystic and solid mass in the left frontal-parietal-temporal region. Histopathologic analysis of resected tumor tissue confirmed the diagnosis of glioblastoma, and comprehensive genomic profiling demonstrated absence of any BRAF or H3F3A mutations. Genomic prof...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
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Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
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Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
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Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: We identified a hyper-mutated subgroup among IDH-wt GBMs in adults < 55 years that had improved prognosis. Two cases were ultra-mutated and characterized by the presence of at least 25% giant cells, MMR mutations, and MSI. Since high TML has been associated with response to immune checkpoint inhibition in paediatric gliomas, the identification of a subtype of ultra-mutated IDH-wt GBM may have implications for immunotherapy.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - Category: Radiology Authors: Tags: Radiother Oncol Source Type: research
In this study, we investigated the mechanism by which the downregulated expression of PER1 promotes theapoptosis of wild-type P53 human glioma U343 cells exposed to X-rays. METHODS: U343 cells were exposed to 6 mV10 Gy X-ray irradiation after infection with an shRNA lentivirus to reduce the expression of PER1 and were analyzedby SCGE analysis, flow cytometry, qRT-PCR, and western blotting. RESULT: SCGE analysis revealed that compared withthe controls, U343 cells expressing low levels of PER1 showed minor DNA damage when exposed to X-ray irradiation(P
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
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