Integrated array CGH and expression profiling revealed candidate biomarkers in gastrointestinal stromal turmor
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE47913 | GEO | 2013/06/14
SECONDARY ACCESSION(S): PRJNA208303
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-06-14 | E-GEOD-47913 | biostudies-arrayexpress
Project description:Gastrointestinal stromal tumors (GISTs) are the most important mesenchymal tumors of the gastrointestinal tract. The vast majority of GISTs exhibit activating mutations of KIT or PDGFRA, but epigenetic alteration of GISTs is largely unknown. In this study, we aimed to clarify the involvement of DNA methylation in GIST malignancy. A total of 25 GIST specimens were studied using Human Genome CGH Microarray Kit 105A (G4412A, Agilent). Levels of LINE-1 methylation were analyzed using bisulfite-pyrosequencing. LINE-1 hypomethylation was correlated with risk grade, and high-risk GISTs exhibited lower levels of LINE-1 methylation than low- or intermediate-risk GISTs. Array CGH analysis revealed a significant correlation between LINE-1 hypomethylation and chromosomal aberrations. Our data suggest that LINE-1 hypomethylation correlates with the aggressiveness of GISTs. Hypomethylation may increase the malignant potential of GISTs by inducing accumulation of chromosomal aberrations.
2010-06-20 | GSE22185 | GEO
Project description:Gastrointestinal stromal tumors (GISTs) comprise a biologically diverse group of neoplasms with respect to activating mutations in either KIT or PDGFRA genes, histology, anatomic site of origin, and clinical aggressiveness. In this study, we applied the high resolution array-based comparative genomic hybridization (array-CGH) technology to 66 primary GISTs (40 gastric and 26 non-gastric, 48 with KIT- and 18 with PDGFRA-mutations) for identification of novel high-level alterations and for characterization of genotype-related genomic changes. All cases had genomic imbalances with the highest occurrence of chromosome 14q (73%), 1p (62%), 22q (59%), 15q (38%) and 13q (29%) losses. Our data indicate that loss of chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of tumor genotype. Furthermore, DNA copy number changes showed a site dependent pattern. These included lower incidence of losses at 14q (87% vs. 35%), and higher frequency of losses at 1p (45%, vs. 85%) and 15q (17% vs. 69%) in non-gastric versus gastric site (p<0.001 for all). However, in the multivariate analysis with adjustment to tumor risk stratification, only the chromosome 14q loss site-dependent pattern of distribution retained its significance. These findings suggest that loss of chromosome 14q is a relatively late genetic event in the development of non-gastric GISTs, the lack of which is most likely substituted by the accumulation of chromosomes 1p/15q and other changes. The novel minimal overlapping regions of deletion at chromosome 1p (1p36.32-1p35.2, 1p34.1, and 1p22.1-1p21.3), 13q (13q14.11-q14.2 and 13q32.3-q33.1) and 15q23 were delineated, which point to chromosomal regions that may harbor genes relevant to the development of these neoplasms. Keywords: comparative genomic hybridization, genotype, site dependent changes
2006-11-08 | GSE5336 | GEO
Project description:To explore mechanisms underlying wild-type GISTs, array CGH was performed on 32 gastric GISTs (4 risk groups stratified by tumor size and mitotic counts comprised 8 cases each).
2013-06-14 | GSE47912 | GEO
Project description:Gastrointestinal stromal tumors (GISTs) are the most important mesenchymal tumors of the gastrointestinal tract. The vast majority of GISTs exhibit activating mutations of KIT or PDGFRA, but epigenetic alteration of GISTs is largely unknown. In this study, we aimed to clarify the involvement of DNA methylation in GIST malignancy. A total of 25 GIST specimens were studied using Human Genome CGH Microarray Kit 105A (G4412A, Agilent). Levels of LINE-1 methylation were analyzed using bisulfite-pyrosequencing. LINE-1 hypomethylation was correlated with risk grade, and high-risk GISTs exhibited lower levels of LINE-1 methylation than low- or intermediate-risk GISTs. Array CGH analysis revealed a significant correlation between LINE-1 hypomethylation and chromosomal aberrations. Our data suggest that LINE-1 hypomethylation correlates with the aggressiveness of GISTs. Hypomethylation may increase the malignant potential of GISTs by inducing accumulation of chromosomal aberrations. A total of 25 surgically obtained human gastrointestinal stromal tumors (GISTs) was analyzed using Agilent CGH microarray. Copy number aberration was compared with clinicopathological features and DNA methylation status.
2010-06-20 | E-GEOD-22185 | biostudies-arrayexpress
Project description:To explore mechanisms underlying wild-type GISTs, array CGH was performed on 32 gastric GISTs (4 risk groups stratified by tumor size and mitotic counts comprised 8 cases each). 27 KIT-mutant, 1 PDGFRA-mutant and 4 wild-type GISTs
2013-06-14 | E-GEOD-47912 | biostudies-arrayexpress
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| S-EPMC3808344 | biostudies-literature
Project description:A Cartes d'Identité des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Affymetrix HG-U133 Plus 2.0 : 46 samples| Agilent SurePrint G3 Human CGH Microarray 4x180K Arrays : 135 samples| To explore the prognostic value of genomic alterations present in primary tumours we perfom a comparative genomic hybridization study on BAC arrays for a panel of breast carcinoma from 45 patients with metastatic relapse and 95 others one, matched for age and axillary node involvement, without any recurrence after 11 years of follow up. Array CGH data was used in establishing a two parameters index representative first of the global level of aneusomy by chromosomal arm and second of the number of breackpoints throughout the genome. Submitter : Nabila Elarouci <elaroucin@ligue-cancer.fr> | Project leader : Michel Longy <longy@bergonie.org>
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-09-04 | E-GEOD-73104 | biostudies-arrayexpress
Project description:Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis, and little molecular evidence exists for its origin, initiation, and progression. The aim of this study was to elucidate candidate molecular pathways involved in tumor pathogenesis.We employed high-throughput array comparative genomic hybridization (aCGH) and cDNA-Mediated Annealing, Selection, Ligation, and Extension Assay to profile the genomic and expression signatures of primary and metastatic ASPS from 17 tumors derived from 11 patients. We used an integrative bioinformatics approach to elucidate the molecular pathways associated with ASPS progression. FISH was performed to validate the presence of the t(X;17)(p11.2;q25) ASPL-TFE3 fusion and, hence, confirm the aCGH observations.FISH analysis identified the ASPL-TFE3 fusion in all cases. aCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify consistent alterations in either group. Gene expression analysis highlighted 1,063 genes that were differentially expressed between the two groups. Gene set enrichment analysis identified 16 enriched gene sets (P < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation. In particular, the paired box transcription factor PAX6 was upregulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6 DNA binding during neural stem cell differentiation.In addition to suggesting a tentative neural line of differentiation for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS.
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