G-Cimp Status Prediction Of Glioblastoma Samples Using mRNA Expression Data

Baysan, Mehmet; Bozdag, Serdar; Cam, Margaret C.; Kotliarova, Svetlana; Ahn, Susie; Walling, Jennifer; Killian, Jonathan Keith; Stevenson, Holly; Meltzer, Paul S.; Fine, Howard A.

doi:10.1371/journal.pone.0047839

Cited by 36 publications

(39 citation statements)

References 17 publications

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“…To facilitate exploration of this dataset, we have made it available through a webportal (http://recur.bioinfo.cnio.es/) associated with GlioVis (Bowman et al, 2017). We used a gene expression signature (Baysan et al, 2012) to determine that 33 of 124 cases were IDHmut or hypermethylated (known as the GCIMP phenotype) at presentation and recurrence (Table S6). We used the renewed gene signatures and classification method to determine molecular subtype of the 91 pairs of IDH-WT cases and found that expression class remained consistent after disease recurrence for 50 of 91 IDH-WT cases (55%) (Figure 5A).…”

Section: Resultsmentioning

confidence: 99%

Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

et al. 2017

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Summary We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8+ T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy.

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Section: Resultsmentioning

confidence: 99%

Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

et al. 2017

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“…S7). Comparison with the G-CIMP classification scheme (14) showed that signatures of G-CIMP+ and G-CIMP− gliomas (24) were enriched in PM and EM gliomas, respectively; subsets of the G-CIMP+ and G-CIMP− signatures were concomitantly enriched in EM low PM low gliomas and control samples (SI Appendix, Fig. S8).…”

Section: Resultsmentioning

confidence: 99%

A glioma classification scheme based on coexpression modules of EGFR and PDGFRA

Sun

Zhang

Chen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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We hypothesized that key signaling pathways of glioma genesis might enable the molecular classification of gliomas. Gene coexpression modules around epidermal growth factor receptor (EGFR) (EM, 29 genes) or platelet derived growth factor receptor A (PDGFRA) (PM, 40 genes) in gliomas were identified. Based on EM and PM expression signatures, nonnegative matrix factorization reproducibly clustered 1,369 adult diffuse gliomas WHO grades II-IV from four independent databases generated in three continents, into the subtypes (EM, PM and EM low PM low gliomas) in a morphology-independent manner. Besides their distinct patterns of genomic alterations, EM gliomas were associated with higher age at diagnosis, poorer prognosis, and stronger expression of neural stem cell and astrogenesis genes. Both PM and EM low PM low gliomas were associated with younger age at diagnosis and better prognosis. PM gliomas were enriched in the expression of oligodendrogenesis genes, whereas EM low PM low gliomas were enriched in the signatures of mature neurons and oligodendrocytes. The EM/PM-based molecular classification scheme is applicable to adult low-grade and high-grade diffuse gliomas, and outperforms existing classification schemes in assigning diffuse gliomas to subtypes with distinct transcriptomic and genomic profiles. The majority of the EM/PM classifiers, including regulators of glial fate decisions, have not been extensively studied in glioma biology. Subsets of these classifiers were coexpressed in mouse glial precursor cells, and frequently amplified or lost in an EM/PM glioma subtypespecific manner, resulting in somatic copy number alteration-dependent gene expression that contributes to EM/PM signatures in glioma samples. EM/PM-based molecular classification provides a molecular diagnostic framework to expedite the search for new glioma therapeutic targets.

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“…Genome-wide methylation studies have uncovered that tumors with enriched methylation in CpG islands have a particularly aggressive phenotype, termed the CpG island methylator phenotype (CIMP) [102]. CIMP was found to predict prognosis and, in some cases, response to therapy in various cancers [103–109]. Tanemura et al investigated promoter methylation of tumor-related genes (TRGs): WIF1, TFPI2, RASSF1A, SOCS1, GATA4, RARB2, and a family of MINT (methylated in tumor) genes in an attempt to define a CIMP in melanoma [34].…”

Section: Differential Dna Methylation As a Biomarker In Melanomamentioning

confidence: 99%

Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities

2017

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Aberrant DNA methylation is an epigenetic hallmark of melanoma, known to play important roles in melanoma formation and progression. Recent advances in genome-wide methylation methods have provided the means to identify differentially methylated genes, methylation signatures, and potential biomarkers. However, despite considerable effort and advances in cataloging methylation changes in melanoma, many questions remain unanswered.The aim of this review is to summarize recent developments, emerging trends, and important unresolved questions in the field of aberrant DNA methylation in melanoma. In addition to reviewing recent developments, we carefully synthesize the findings in an effort to provide a framework for understanding the current state and direction of the field. To facilitate clarity, we divided the review into DNA methylation changes in melanoma, biomarker opportunities, and therapeutic developments. We hope this review contributes to accelerating the utilization of the diagnostic, prognostic, and therapeutic potential of DNA methylation for the benefit of melanoma patients.

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G-Cimp Status Prediction Of Glioblastoma Samples Using mRNA Expression Data

Cited by 36 publications

References 17 publications

Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment

A glioma classification scheme based on coexpression modules of EGFR and PDGFRA

Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities

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