Gene Expression Profiles Associated with Treatment Response in Oligodendrogliomas

French, Pim J.; Swagemakers, Sigrid; Nagel, Jord H.A.; Kouwenhoven, Mathilde C.M.; Brouwer, Eric; Spek, Peter van der; Luider, Theo M.; Kros, Johan M.; Bent, Martin J. van den; Smitt, Peter A. Sillevis

doi:10.1158/0008-5472.can-05-1886

Cited by 103 publications

(85 citation statements)

References 51 publications

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“…Two previous studies have reported similar comparisons of genotype and gene expression in oligodendroglial tumors [7,25]. French et al reported 60 genes associated with 1p/19q loss and Mukasa et al reported 209 genes associated with 1p loss; only a few of the genes identified were differentially expressed in this study.…”

Section: Discussionsupporting

confidence: 72%

“…Of these, neuronal intermediate filament protein, alphainternexin (INA) and the scaffold protein IQGAP1 have been investigated in other glioma studies [6,7], while the steroid/thyroid hormone receptor, NR2F2 and the transforming growth factor beta inhibiting protein, TGIF1, represent novel findings of differential expression in gliomas. Three genes on 1p, down-regulated approximately two-fold, are of note.…”

Section: Discussionmentioning

confidence: 99%

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Gene expression in oligodendroglial tumors

et al. 2011

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Abstract.Background: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity.Methods: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy (26 serial stereotactic biopsy, 2 resection). Expression of differentially expressed genes was validated by real-time PCR.Results: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy included SSBP2, GFRA1, FAP and RASD1. IQGAP1, INA, TGIF1, NR2F2 and MYCBP were differentially expressed in oligodendroglial tumors with 1p/19q loss.Conclusion: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Gene expression in oligodendroglial tumors

et al. 2011

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“…Data from Refs. 43-50 were reanalyzed to show expression level of Emi1 in normal brain, glioblastoma, oligodendroglioma, anaplastic oligodendroglioma, astrocytoma, head and neck cancer, breast cancer, pancreatic ductal adenocarcinoma, cervical cancer, transitional cell carcinoma, and adult male germ cell tumor (43)(44)(45)(46)(47)(48)(49)(50). N, normal tissues; T, tumor tissues.…”

Section: Emi1 Knockdown Enhances the Induction Of Apoptosis By Doxorumentioning

confidence: 99%

Selective Enhancing Effect of Early Mitotic Inhibitor 1 (Emi1) Depletion on the Sensitivity of Doxorubicin or X-ray Treatment in Human Cancer Cells

Shimizu

Nakajima²,

Takemoto

et al. 2013

Journal of Biological Chemistry

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Background:To improve the effectiveness of chemo-and radiotherapy only in cancer tissue is important for avoiding side effects. Results: Emi1 depletion enhanced the sensitivity of anticancer reagents and X-ray irradiation in cancer cells. Conclusion: Emi1 siRNA would be a useful new modality for enhancing the effect of chemo-and radiotherapy in various tumors. Significance: This work provides new insights regarding synergistic effect of Emi1 knockdown in combination therapies.

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“…Microsatellites were amplified by PCR on 20 nanogram genomic DNA, using a fluorescently labeled forward primer and a reversed primer. Allelic losses were statistically determined as described and scored by two independent researchers (French et al, 2005). TP53 (NM_000546.4, GI:187830767) status was determined in 169 samples.…”

Section: Samplesmentioning

confidence: 99%

Segregation of non-p.R132H mutations inIDH1in distinct molecular subtypes of glioma

et al. 2010

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Mutations in the gene encoding the isocitrate dehydrogenase 1 gene (IDH1) occur at a high frequency (up to 80%) in many different subtypes of glioma. In this study, we have screened for IDH1 mutations in a cohort of 496 gliomas. IDH1 mutations were most frequently observed in low grade gliomas with c.395G>A (p.R132H) representing >90% of all IDH1 mutations. Interestingly, non-p.R132H mutations segregate in distinct histological and molecular subtypes of glioma. Histologically, they occur sporadically in classic oligodendrogliomas and at significantly higher frequency in other grade II and III gliomas. Genetically, non-p.R132H mutations occur in tumors with TP53 mutation, are virtually absent in tumors with loss of heterozygosity on 1p and 19q and accumulate in distinct (gene-expression profiling based) intrinsic molecular subtypes. The IDH1 mutation type does not affect patient survival. Our results were validated on an independent sample cohort, indicating that the IDH1 mutation spectrum may aid glioma subtype classification. Functional differences between p.R132H and non-p.R132H mutated IDH1 may explain the segregation in distinct glioma subtypes.

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Gene Expression Profiles Associated with Treatment Response in Oligodendrogliomas

Abstract: Oligodendrogliomas are a specific subtype of brain tumor of which the majority responds favorably to chemotherapy.

Cited by 103 publications

References 51 publications

Gene expression in oligodendroglial tumors

Gene expression in oligodendroglial tumors

Selective Enhancing Effect of Early Mitotic Inhibitor 1 (Emi1) Depletion on the Sensitivity of Doxorubicin or X-ray Treatment in Human Cancer Cells

Segregation of non-p.R132H mutations inIDH1in distinct molecular subtypes of glioma

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