Integrated Array-Comparative Genomic Hybridization and Expression Array Profiles Identify Clinically Relevant Molecular Subtypes of Glioblastoma

Nigro, Janice; Misra, Ankita; Zhang, Li; Смирнов, Иван; Colman, Howard; Griffin, Chandi; Ozburn, Natalie; Chen, Mingang; Pan, Edward; Koul, Dimpy; Yung, W. K. Alfred; Feuerstein, Burt G.; Aldape, Kenneth

doi:10.1158/0008-5472.can-04-2921

Cited by 293 publications

(307 citation statements)

References 33 publications

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“…These independent methods of determining gene expression levels additionally validate our findings. High YKL-40 mRNA expression was significantly associated with poorer survival; moreover, they demonstrated that YKL-40-transfected immortalized human astrocytes consistently showed increased resistance to radiation and a fivefold induction in invasive potential as compared with control cells (Nigro et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization

et al. 2005

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Glioblastoma (GBM) is a highly malignant glioma, which has the propensity to infiltrate throughout the brain in contrast to pilocytic astrocytoma (PA) of the posterior fossa, which does not spread and can be cured by surgery. We have used Suppression Subtractive Hybridization to define markers that better delineate the molecular basis of brain invasion and distinguish these tumor groups. We have identified 106 genes expressed in PA versus GBM and 80 genes expressed in GBM versus PA. Subsequent analysis identified a subset of 20 transcripts showing a common differential expression pattern for the two groups. GBM differs from PA by the expression of five genes involved in invasion and angiogenesis: fibronectin, osteopontin, chitinase-3-like-1 (YKL-40), keratoepithelin and fibromodulin. PA differs from GBM by the expression of genes related to metabolism (apolipoprotein D), proteolysis (protease-serine-11), receptor and signal transduction (PLEKHB1 for Pleckstrin-Homology-domain-containingprotein-family-B-member-1), transcription/translation (eukaryotic-translation-elongation-factor-1-a1) processes and cell adhesion (SPOCK1 for SPARC/Osteonectin-CWCV-kazal-like-domains-proteoglycan). The expression of these genes was confirmed by real-time quantitative RT-PCR and immunohistochemistry. This study highlights the crucial role of brain invasion in GBM and identifies specific molecules involved in this process. In addition, it offers a restricted list of markers that accurately distinguish PA from GBM.

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Section: Discussionmentioning

confidence: 99%

Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization

et al. 2005

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“…Similarly, other studies found that 10q loss was associated with reduced progression free or OS in patients with oligodendroglial tumors 11,22 or glioblastomas. 39,40 One of the likely targets on 10q is the PTEN tumor suppressor gene at 10q23.3, as supported by studies showing that PTEN mutation was indicative of poor outcome in anaplastic oligodendrogliomas. 11,23 Our finding that gains of 19q and 20 were associated with shorter survival in oligodendroglial tumors is paralleled by results in glioblastomas demonstrating that 19q and 20 gains were more frequent in the group of short-term survivors.…”

Section: Discussionmentioning

confidence: 99%

Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors

Trost

Ehrler

Fimmers

et al. 2007

Intl Journal of Cancer

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Deletions on chromosomes 1p and 19q are associated with favorable prognosis in patients with oligodendroglial tumors. The aim of our study was to identify additional genomic aberrations linked to patient survival. We performed a genome‐wide screen for genomic imbalances by comparative genomic hybridization on tumors from 70 patients, including 40 oligodendrogliomas, 30 oligoastrocytomas (21 WHO grade II tumors, 49 WHO grade III tumors). Data were correlated with overall patient survival (OS, median follow‐up: 5.8 years). The most frequent aberrations were losses on chromosome 19q (64%), 1p (59%), 9p (26%), 4q (21%), 10q (19%), 18q (17%); gains on 7q (24%), 19p (19%), 7p (17%). In univariate analyses, combined 1p/19q and 19q loss were significantly associated with longer OS, and gains on 7, 8q, 19q, 20, losses on 9p, 10, 18q, Xp with shorter OS. Multivariate analyses showed the most significant prognostic factors for OS of patients with any oligodendroglial tumor to be WHO grade [odds ratio (OR) 8], 7p gain (OR 6), 9p loss (OR 3); for OS of patients with anaplastic tumors to be 7p gain (OR 10), 8q gain (OR 5), 18q loss (OR 3). Patients with anaplastic oligodendroglial tumors containing one or more prognostically unfavorable genomic aberration had a poor outcome independent of the 1p/19q status. In summary, we identified several independent genomic markers of shorter survival in patients with oligodendroglial tumors. Thus, molecular diagnostic testing, which is usually restricted to 1p/19q deletion analysis, may need to be refined by additionally assessing the prognostically unfavorable genomic aberrations identified. © 2007 Wiley‐Liss, Inc.

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“…Several works (Sallinen et al, 2000;Khan et al, 2001;Ramaswamy et al, 2001;Rickman et al, 2001;Agrawal et al, 2002;Kim et al, 2002;Veer et al, 2002;Vijver et al, 2002;Boom et al, 2003;Godard et al, 2003;Hunter et al, 2003;Mischel et al, 2003;Nutt et al, 2003;Shai et al, 2003;Sorlie et al, 2003;Freije et al, 2004;Mischel et al, 2004;Hoelzinger et al, 2005;Liang et al, 2005;Nigro et al, 2005;Rich et al, 2005;Somasundaram et al, 2005;Wong et al, 2005) showed the usefulness of utilizing methods of analysis of multiple forms of data including both clinical and multiple genes, to achieve a more precise discrimination of outcomes for individual patients. The same logical use of multiple forms of data and methods of analysis has been applied in the present study to accurately achieve better classification and prediction of glioma patients.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, developed microarray technology has permitted development of multi-organ cancer classification including gliomas (Ramaswamy et al, 2001;Rickman et al, 2001;Kim et al, 2002;Hunter et al, 2003;Mischel et al, 2004), identification of tumor subclasses (Khan et al, 2001;Mischel et al, 2003;Shai et al, 2003;Sorlie et al, 2003;Liang et al, 2005;Nigro et al, 2005;Wong et al, 2005), discovery of progression markers (Sallinen et al, 2000;Agrawal et al, 2002;van de Boom et al, 2003;Godard et al, 2003;Hoelzinger et al, 2005;Rich et al, 2005;Somasundaram et al, 2005) and prediction of disease outcomes (van't Veer et al, 2002;van de Vijver et al, 2002;Nutt et al, 2003;Freije et al, 2004). Unlike clinicopathological staging, molecular staging can predict long-term outcomes of any individual based on gene expression profile of the tumor at diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Identification of expressed genes characterizing long-term survival in malignant glioma patients

Arao²,

et al. 2006

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Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of high-grade gliomas in a more objective manner than standard pathology. RNAs from 29 malignant gliomas were analysed using Agilent microarrays. We identified 21 genes whose expression was most strongly and consistently related to patient survival based on univariate proportional hazards models. In six out of 10 genes, changes in gene expression were validated by quantitative real-time PCR. After adjusting for clinical covariates based on a multivariate analysis, we finally obtained a statistical significance level for DDR1 (discoidin domain receptor family, member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was confirmed that DDR1 protein expression was also correlated to the prognosis of glioma patients detected by immunohistochemical staining. Furthermore, we analysed the efficacy of the short interfering RNA (siRNA)-mediated inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1 can be a novel molecular target of therapy as well as an important predictive marker for survival in patients with glioma. Our method was effective at classifying highgrade gliomas objectively, and provided a more accurate predictor of prognosis than histological grading.

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Integrated Array-Comparative Genomic Hybridization and Expression Array Profiles Identify Clinically Relevant Molecular Subtypes of Glioblastoma

Cited by 293 publications

References 33 publications

Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization

Identification of genes differentially expressed in glioblastoma versus pilocytic astrocytoma using Suppression Subtractive Hybridization

Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors

Identification of expressed genes characterizing long-term survival in malignant glioma patients

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