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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).

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Amandine Etcheverry

PROVIDER: E-MTAB-5098 | 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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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).

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. 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.

2016-09-19 | E-MTAB-5109 | biostudies-arrayexpress

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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.

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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

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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

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Esophageal cancer intratumor heterogeneity revealed by multi-region whole exome sequencing and aCGH

Project description:Cancer is a disease of the genome. Many genomic abnormalities have been found in a variety of cancer types, which are believed to be attributable to tumorigenesis as well as resistance to treatment and recurrence. Genomic heterogeneity in the same type of cancer or within a tumor reveals the complexity of cancer biology so that intratumor heterogeneity has become an inherent feature of cancer. In this study, we use whole-exome sequencing and array comparative genomic hybridization technology to examine the mutational profiling and copy number changes from multi-region samples within an esophageal cancer in order to understand the genomic phylogeny in the evolution of intratumor heterogeneity in esophageal cancer.

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