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Methylome profiling of glioblastoma biopsies obtained by neuro-navigation in four distinct areas for 10 patients (necrotic zone, tumor zone, interface, and peripheral brain zone).

ABSTRACT: We classified samples and deciphered a key genes signature of intratumor heterogeneity by Principal Component Analysis and Weighted Gene Co-expression Network Analysis. We provide a signature of key cancer-heterogeneity genes highly associated with the intratumor spatial gradient and show that it is enriched in genes with correlation between methylation and expression levels.

ORGANISM(S): Homo sapiens

SUBMITTER: Amandine Etcheverry

PROVIDER: E-MTAB-5109 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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From the core to beyond the margin: a genomic picture of glioblastoma intratumor heterogeneity.

Aubry Marc M de Tayrac Marie M Etcheverry Amandine A Clavreul Anne A Saikali Stéphan S Menei Philippe P Mosser Jean J

Oncotarget 20150501 14

Glioblastoma (GB) is a highly invasive primary brain tumor that almost systematically recurs despite aggressive therapies. One of the most challenging problems in therapy of GB is its extremely complex and heterogeneous molecular biology. To explore this heterogeneity, we performed a genome-wide integrative screening of three molecular levels: genome, transcriptome, and methylome. We analyzed tumor biopsies obtained by neuro-navigation in four distinct areas for 10 GB patients (necrotic zone, tu ...[more]

PMID: 25940437

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Transcriptome profiling of glioblastoma biopsies obtained by neuro-navigation in four distinct areas for 10 patients (necrotic zone, tumor zone, interface, and peripheral brain zone).

Project description:We classified samples and deciphered a key genes signature of intratumor heterogeneity by Principal Component Analysis and Weighted Gene Co-expression Network Analysis. Transcriptome analysis highlighted a pronounced intratumor architecture reflecting the surgical sampling plan of the study and identified gene modules associated with hallmarks of cancer.

2016-09-19 | E-MTAB-5092 | biostudies-arrayexpress

aCGH profiling of glioblastoma biopsies obtained by neuro-navigation in four distinct areas for 10 patients (necrotic zone, tumor zone, interface, and peripheral brain zone).

Project description:We classified samples and deciphered a key genes signature of intratumor heterogeneity by Principal Component Analysis and Weighted Gene Co-expression Network Analysis. At the genome level, we identified common GB copy number alterations and but a strong inter-individual molecular heterogeneity.

2016-09-19 | E-MTAB-5098 | biostudies-arrayexpress

Epigenetic portraits of human breast cancers (HCT116 cell line data)

Project description:Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known “expression subtypes” but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients. 6 methylation profiling of HCT116 cell lines. Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.

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DNA Methylation Profiling of Glioblastoma: Impact on Gene Expression and Clinical Outcome (Illumina)

Project description:Genome-scale measurements of DNA methylation levels are necessary to decipher the epigenetic events involved in glioblastoma aggressive phenotype, and to guide new therapeutic strategies. In that purpose, we performed a whole genome integrative analysis of the methylation and expression profiles for 40 newly diagnosed glioblastoma patients. We have also screened for associations between CpG sites methylation levels and overall survival in a cohort of 50 patients uniformly treated with radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter being differentially expressed in a concordant way. Among these concordant CpG sites, 13 genes displayed, within our glioblastoma cohort, an inverse correlation between promoter methylation and expression levels: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. The expression of these genes may be tightly regulated by epigenetic mechanisms. The survival analysis identified six CpG sites associated with overall survival. The SOX10 promoter methylation status (two CpG sites) stratifies the patients in a way similar to MGMT with improved performance based on Area Under the Curve criteria (0.78 vs. 0.71, p-value < 5.10-4). The methylation status of FNDC3B, TBX3, DGKI, and FSD1 promoters identify patients with MGMT methylated tumors non-responding to STUPP treatment (p-value < 1.10-4). These markers have a potential impact on therapeutic decision. 55 glioblastoma samples and 3 control brain samples were analysed.

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2011-10-18 | E-GEOD-22249 | biostudies-arrayexpress

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Project description:Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimising treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but information is scant on the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease. Here we used the Infinium Methylation Platform to profile at single-CpG resolution (over 14,000 genes interrogated) the methylomes of 119 breast tumours. It emerges that many genes whose expression is linked to the ER status are epigenetically controlled (or/ we show that the two major phenotypes of breast cancers determined by ER status are widely involving epigenetic regulatory mechanisms), offering the prospect of a novel approach to treating ER-positive tumours. We have distinguished methylation-profile-based tumour clusters, some coinciding with known “expression subtypes” but also new entities that may provide a meaningful basis for refining breast tumour typology. We show that methylation patterns may reflect the cellular origins of tumours. Having highlighted an unexpectedly strong epigenetic component in the regulation of key immune pathways, we show that a set of immune genes have high prognostic value in specific tumour categories. By laying the ground for better understanding of breast cancer heterogeneity and improved tumour taxonomy, the precise epigenetic portraits drawn here should contribute to better management of breast cancer patients. 123 gene expression profiling breast cancer patients. Study of epigenetic variation (methylation) linked to gene expression. No replicate, no reference sample.

2011-10-18 | E-GEOD-20712 | biostudies-arrayexpress

Transcription profiling of human cervical cancer patient biopsies to explore intratumour heterogeneity reveals that intratumor variation is low for most probe sets tested but that multiple biopsies are recommended for reliable estimates of gene expression

Project description:To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. Experimental Design: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor.The extracted RNA was hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T =W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values.

2007-11-11 | E-GEOD-5787 | biostudies-arrayexpress

Survey of Intra- and Inter-Tumour Heterogeneity of Gene Expression in Cervical Cancer

Project description:Purpose: To explore intratumor heterogeneity in gene expression profiles from patients with cervical cancer. Experimental Design: A total of 33 biopsies were obtained from 11 patients, sampling between two and five different areas for each tumor.The extracted RNAwas hybridized onto the Affymetrix U133 Plus 2.0 oligonucleotide chip. The variance of expression within a patient (W), between patients (B) and the total variance (T =W + B) were calculated for each ProbeSet, and the ratio W/T was used as a measure of intratumor heterogeneity. Gene Ontology functional analysis was done to assess the function of genes that had high W/T (top 10%) and low W/T (bottom 10%) values. Results: In total, 448 ProbeSets (2.2% of the total) had W/T < 0.10, indicating low intratumor heterogeneity, and 537 ProbeSets (2.7% of the total) had W/T > 0.90, indicating high intratumor heterogeneity. In total 14,473 ProbeSets (72.4%) had higher intertumor than intratumor heterogeneity (W/T < 0.5). Genes with low intratumor heterogeneity were characterized by a statistically significant enrichment of immune-related functions (P < 0.0001). Genes with high intratumor heterogeneity were characterized by a significant tendency towards nuclear localization and nucleic acid binding (both P < 0.0001). For genes with W/T > 0.5, more than six biopsies would be required to minimize the intratumoral heterogeneity to <0.15; if W/T is 0.3 to 0.4, four biopsies are required; and for low W/T of 0.16 to 0.3, only two to three biopsies would be needed. Conclusion: Although the intratumor heterogeneity was low for the majority of the tested ProbeSets, for many genes, multiple biopsies are required to obtain a reliable estimate of gene expression. Keywords: disease state comparison

2006-10-01 | GSE5787 | GEO

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2020-01-16 | E-MTAB-5905 | biostudies-arrayexpress

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