Array Comparative Genomic Hybridization of Pancreatic Xenografts and Cell Lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Alan Shain
PROVIDER: E-GEOD-25273 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Array Comparative Genomic Hybridization (aCGH) of 70 pancreatic ductal adenocarcinoma (PDAC) samples was performed on Agilent 244K CGH arrays in order to find common genomic aberrations for cancer gene discovery. Additionally, matched expression profiling on Agilent 44K arrays was performed. Common copy number aberrations were identified in order to identify a list of putative cancer genes. Expression profiling data was used to further enrich this list of putative cancer genes for more likely candidates. Last, the most promising candidates were functionally interrogated using RNA interference-mediated knockdown to mimic loss. Well-known PDAC cancer genes were observed as amplified (KRAS and MYC) and deleted (CDKN2A, TGFBR2, SMAD4, and MAP2K4).
2011-12-15 | GSE25273 | GEO
Project description:Expression profiling of 70 Pancreatic Ductal Adenocarcinoma (PDAC) samples was performed on Agilent 44K expression arrays for cancer gene discovery. Additionally, matched aCGH on Agilent 244K arrays was performed. These two datasets were integrated in order to identify driver mutations leading to pancreatic cancer. Promising candidates were interrogated further using functional studies. 68 tumor samples (48 xenografts, 20 cell lines). 2 color arrays hybridized against a common reference pool of RNA from 11 cancer cell lines
2011-12-15 | E-GEOD-26088 | biostudies-arrayexpress
Project description:Expression profiling of 70 Pancreatic Ductal Adenocarcinoma (PDAC) samples was performed on Agilent 44K expression arrays for cancer gene discovery. Additionally, matched aCGH on Agilent 244K arrays was performed. These two datasets were integrated in order to identify driver mutations leading to pancreatic cancer. Promising candidates were interrogated further using functional studies.
2011-12-15 | GSE26088 | GEO
Project description:Background/Aims: Microarray-based comparative genomic hybridisation (CGH) has allowed high-resolution analysis of DNA copy number alterations across the entire cancer genome. Recent advances in bioinformatics tools enable us to perform a robust and highly sensitive analysis of array CGH data and facilitate the discovery of novel cancer-related genes. Methods: We analysed a total of 29 pancreatic ductal adenocarcinoma (PDAC) samples (six cell lines and 23 microdissected tissue specimens) using 1 Mb-spaced CGH arrays. The transcript levels of all genes within the identified regions of genetic alterations were then screened using our Pancreatic Expression Database. Results: In addition to 238 high-level amplifications and 35 homozygous deletions, we identified 315 minimal common regions of “non-random” genetic alterations (115 gains and 200 losses) which were consistently observed across our tumour samples. The small size of these aberrations (median size of 880 kb) contributed to the reduced number of candidate genes included (on average 12 Ensembl-annotated genes). The database has further specified the genes whose expression levels are consistent with their copy number status. Such genes were UQCRB, SQLE, DDEF1, SLA, ERICH1 and DLC1, indicating that these may be potential target candidates within regions of aberrations. Conclusion: This study has revealed multiple novel regions that may indicate the locations of oncogenes or tumour suppressor genes in PDAC. Using the database, we provide a list of novel target genes whose altered DNA copy numbers could lead to significant changes in transcript levels in PDAC. (Harada et al. Pancreatology) Keywords: pancreatic ductal adenocarcinima, tissue microdissection, array CGH, genetic alterations A panel of 23 microdissected PDAC tissues and 6 PDAC-derived cell lines were analysed using Sanger's CGH arrays with 1 Mb resolution. Clinical info of the samples used is provided as a supplementary file.
2008-12-16 | E-GEOD-9672 | biostudies-arrayexpress
Project description:The array comparative genomic hybridization (aCGH) was perform to identify regions with genomic imbalance in lung cancer.The aCGH analysis detected a total of 325 regions with genomic imbalance in all 8 lung cancer samples, ranging from focal rearrangements (70 kb–5 Mb) to chromosome-arm alterations with chromosomal segments amplification or deletion. Among these mutations, a total of 115 genomic imbalances were discovered occurring at high frequency varying from 25% to 50%.
2016-11-17 | GSE89927 | GEO
Project description:Background/Aims: Microarray-based comparative genomic hybridisation (CGH) has allowed high-resolution analysis of DNA copy number alterations across the entire cancer genome. Recent advances in bioinformatics tools enable us to perform a robust and highly sensitive analysis of array CGH data and facilitate the discovery of novel cancer-related genes. Methods: We analysed a total of 29 pancreatic ductal adenocarcinoma (PDAC) samples (six cell lines and 23 microdissected tissue specimens) using 1 Mb-spaced CGH arrays. The transcript levels of all genes within the identified regions of genetic alterations were then screened using our Pancreatic Expression Database. Results: In addition to 238 high-level amplifications and 35 homozygous deletions, we identified 315 minimal common regions of “non-random” genetic alterations (115 gains and 200 losses) which were consistently observed across our tumour samples. The small size of these aberrations (median size of 880 kb) contributed to the reduced number of candidate genes included (on average 12 Ensembl-annotated genes). The database has further specified the genes whose expression levels are consistent with their copy number status. Such genes were UQCRB, SQLE, DDEF1, SLA, ERICH1 and DLC1, indicating that these may be potential target candidates within regions of aberrations. Conclusion: This study has revealed multiple novel regions that may indicate the locations of oncogenes or tumour suppressor genes in PDAC. Using the database, we provide a list of novel target genes whose altered DNA copy numbers could lead to significant changes in transcript levels in PDAC. (Harada et al. Pancreatology) Keywords: pancreatic ductal adenocarcinima, tissue microdissection, array CGH, genetic alterations
2008-12-17 | GSE9672 | GEO
Project description:To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations.
2019-02-05 | GSE126053 | GEO
Project description:The newly discovered 5-hydroxymethylcytosine (5hmC) may complicate previous observations of abnormal cytosine methylation statuses used for the identification of new tumor suppressor gene candidates relevant to human hepatocarcinogenesis. The simultaneous detection of 5mC and 5hmC will stimulate the discovery of aberrantly methylated genes with increased accuracy in human hepatocellular carcinoma (HCC). Here, we performed a newly developed single-base high-throughput sequencing approach (hydroxymethylation and methylation Sensitive Tag sequencing, HMST-seq) to synchronously measure these two modifications in HCC samples. After identifying the differentially methylated and hydroxymethylated genes in HCC, we integrated the DNA copy-number alterations as determined using array-based comparative genomic hybridization (aCGH) data with gene expression to identify genes potentially silenced by promoter hypermethylation. As a result, we report a high enrichment of genes with epigenetic aberrations in cancer signaling pathways. Six genes were selected as tumor suppressor gene (TSG) candidates, among which, ECM1, ATF5 and EOMES were confirmed to have potential anti-cancer function via siRNA experiments.
2014-09-01 | GSE54141 | GEO
Project description:Characterized by a wide histological spectrum, myxofibrosarcoma ranges from deceptively bland-appearing lesions to frankly pleomorphic sarcomas, representing a suitable model to elucidate the molecular aberrations in multistep disease progression. To explore cancer-associated genes of myxofibrosarcoma, ultrahigh-resolution array comparative genomic hybridization (aCGH) was used to profile DNA copy number alterations in myxofibrosarcoma tumor samples and cell lines.
2012-02-02 | GSE35483 | GEO
Project description:Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic infor- mation. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC sub- group, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differ- ences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male- simple subgroup appears notably different from any geno- mic subgroup so far defined in FBC. Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic infor- mation. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC sub- group, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differ- ences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male- simple subgroup appears notably different from any geno- mic subgroup so far defined in FBC. Tumor cellularity was determined on H&E-stained sections and only tumors with high tumor cell content were included. DNA was extracted from fresh frozen tissue using a modification of a back-extraction protocol from the organic phase of the Qiagen Lipid mini RNA kit (Qiagen, Valencia, CA) as follows: 1 M Tris-buffer containing 4 M Guanidine Thiocyanate and 50 mM Sodium Citrate, followed by glycogen precipitation. DNA quality was assessed with a BioAnalyzer. Sufficient good quality DNA from 56 fresh frozen MBC tumors was available for high-resolution tiling BAC aCGH. BAC arrays, containing about 32,000 BAC clones mapped to the UCSC Human Genome build 17, were produced at the SCIBLU Genomics Resource Center, Lund University, Sweden. The aCGH data were normalized using PopLowess. Circular binary segmentation (CBS) was used for breakpoint analysis with an a of 0.01 and segments containing at least four probes were used in subsequent analyses.
2016-07-03 | E-GEOD-50512 | biostudies-arrayexpress