Gene dosage and mutational analyses of EGFR in oligodendrogliomas

Franco-Hernandez, Carmen; Martinez-Glez, Víctor; Alonso, M. Eva; Campos, José M. de; Isla, Alberto; Vaquero, Jesús; Gutiérrez, Manuel; Rey, Juan A.

doi:10.3892/ijo.30.1.209

Cited by 15 publications

(20 citation statements)

References 22 publications

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“…Multiplex ligation‐dependent probe amplification (MLPA) was used for determining allelic losses and gains of the gene in the tumor samples. The analysis was performed using the SALSA MLPA kit P088‐B1 and P105‐C1 in accordance with the manufacturer's protocol (MRC Holland, Amsterdam, the Netherlands) . All the procedures were performed as described previously …”

Section: Methodsmentioning

confidence: 99%

Immunohistochemical analysis‐based proteomic subclassification of newly diagnosed glioblastomas

et al. 2012

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Recent gene expression and copy number profilings of glioblastoma multiforme (GBM) by The Cancer Genome Atlas (TCGA) Research Network suggest the existence of distinct subtypes of this tumor. However, these approaches might not be easily applicable in routine clinical practice. In the current study, we aimed to establish a proteomics‐based subclassification of GBM by integrating their genomic and epigenomic profiles. We subclassified 79 newly diagnosed GBM based on expression patterns determined by comprehensive immunohistochemical observation in combination with their DNA copy number and DNA methylation patterns. The clinical relevance of our classification was independently validated in TCGA datasets. Consensus clustering identified the four distinct GBM subtypes: Oligodendrocyte Precursor (OPC) type, Differentiated Oligodendrocyte (DOC) type, Astrocytic Mesenchymal (AsMes) type and Mixed type. The OPC type was characterized by highly positive scores of Olig2, PDGFRA, p16, p53 and synaptophysin. In contrast, the AsMes type was strongly associated with strong expressions of nestin, CD44 and podoplanin, with a high glial fibrillary acidic protein score. The median overall survival of OPC‐type patients was significantly longer than that of the AsMes‐type patients (19.9 vs 12.8 months). This finding was in agreement with the Oncomine analysis of TCGA datasets, which revealed that PDGFRA and Olig2 were favorable prognostic factors and podoplanin and CD44 were associated with a poor clinical outcome. This is the first study to establish a subclassification of GBM on the basis of immunohistochemical analysis. Our study will shed light on personalized therapies that might be feasible in daily neuropathological practice. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02377.x, 2012)

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Section: Methodsmentioning

confidence: 99%

Immunohistochemical analysis‐based proteomic subclassification of newly diagnosed glioblastomas

et al. 2012

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“…The analysis was performed using the SALSA MLPA KIT P088-B1 and P105-C1 in accordance with the manufacturer's protocol (MRC Holland, Amsterdam, Netherland). [12][13][14][15] Information regarding the probe sequences and ligation sites can be found at www.mlpa.com. Amplification products were separated on an ABI V R 3130 Â I Genetic Analyzer (Applied Biosystems, Foster City, CA) and quantified with Genemapper 4.0 software (Applied Biosystems).…”

Section: Multiplex Ligation-dependent Probe Amplificationmentioning

confidence: 99%

Benefits of interferon‐β and temozolomide combination therapy for newly diagnosed primary glioblastoma with the unmethylated MGMT promoter

Motomura

Natsume

Kishida

et al. 2010

Cancer

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BACKGROUND:The aim of the current study was to catalog genomic and epigenomic abnormalities in newly diagnosed glioblastoma patients and determine the correlation among clinical, genetic, and epigenetic profiles and clinical outcome. METHODS: This study retrospectively included 68 consecutive patients who underwent surgical treatment and received standard radiotherapy with temozolomide (TMZ)-based chemotherapy. Of a total of 68 patients, 39 patients (57.4%) received interferon (IFN)-b in combination of TMZ. RESULTS: The genetic and epigenetic alterations frequently observed were EGFR amplification (51.5%), TP53 mutation (33.8%), CDKN2A loss (32.4%), TP53 loss (16.2%), methylation of the MGMT promoter (33.8%) and IDH1 mutation (5.9%). Multivariate analysis revealed that methylated MGMT promoter and the combination of TMZ and IFN-b were independent prognostic factors associated with survival. The median survival time (MST) of the patients who received the combination of IFN-b and TMZ was significantly greater with 19.9 months as compared to the TMZ alone group (12.7 months). Notably, in even patients whose tumors had unmethylated MGMT promoter, the MST prolonged to 17.2 months when receiving TMZ with IFN-b, compared to 12.5 months in those receiving TMZ without IFN-b. CONCLUSIONS: Taken together, addition of IFN-b for newly diagnosed primary GBM achieved a favorable outcome, particularly in patients with unmethylated MGMT promoter.

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“…Malignant progression is associated with additional genetic abnormalities that are similar to those described above for astrocytomas, including a lack of the RB1 pathway, loss of RB1, or gene amplification/overexpression of the CDK4 gene (Franco-Hernandez et al, 2007;Reifenberger & Louis, 2003).…”

Section: Oligodendrogliomasmentioning

confidence: 95%