Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events [array component]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Peter Haverty
PROVIDER: E-GEOD-40908 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-04-07 | E-GEOD-23056 | biostudies-arrayexpress
Project description:All cancers are diseases of the genome. A combination of somatic point mutations, focal amplifications and deletions, and chromosome level aberrations conspire to disrupt gene expression and the interplay between signaling pathways that control normal growth and tissue homeostasis. Here we investigate somatic copy number abberations in metastatic melanomas. A metastatic melanoma was assayed on Affymetrix SNP arrays to detect copy number abberations. 7 cutaneous melanomas as well as their matched control ( peripheral blood lymphocytes (PBL) or Epstein-Barr virus transformed lymphoblastoid cell lines ) and 2 control melanocytes were assayed on Illumina SNP arrays. 7 metastatic melanomas were hybridized on Agilent CGH arrays using donor matched control as reference.
2011-04-07 | E-GEOD-22928 | biostudies-arrayexpress
Project description:Many preclinical therapy studies have focused on a small number of well-described mouse allograft or human xenograft models that poorly represent the heterogeneity of human disease. Here we have assembled a panel of mouse mammary cell lines derived from spontaneously-arising mouse mammary tumors or from mammary tumors arising in genetically engineered mouse models. We used the Affymetrix Mouse Diversity Genotyping Array to address DNA copy number variation in the genomes of the cell lines of this panel. The resulting information about regions of amplification and deletion should help inform biological analyses as well as provide a reference for cell line authentication/identification. Affymetrix Mouse Diversity Genotyping arrays were used according to manufacturer's directions to analyze gDNA extracted from 27 mouse mammary cell lines of varying malignancy.
2016-06-15 | E-GEOD-69902 | biostudies-arrayexpress
Project description:We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genome of 212 medulloblastomas, a malignant pediatric brain tumor. Focal amplifications of fifteen known oncogenes and focal deletions of twenty known tumor suppressor genes (TSG) were revealed, most not previously implicated in medulloblastoma. Importantly, we identified novel amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determining stem cell fates, and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing, and blocking the state of histone lysine methylation, particularly H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma. Keywords: Affymetrix SNP array Genomic DNA isolated from fresh frozen primary human medulloblastomas and medulloblastoma cell lines were subjected to SNP genotyping using either Affymetrix 100K or 500K GeneChip Mapping array sets for the purpose of obtaining genome-wide copy number and LOH profiles.
2010-04-06 | E-GEOD-14437 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assesed to described chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (60% of cases) in the 7p22.3-p21.1 and 7p15.3-p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2-p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh frozen, and paraffin embedded lung tumor samples Copy number analysis of Affymetrix 500K SNP arrays was performed for 33 lung tumor samples, including lung precursor metaplasia, lung tumors and cell lines. Six samples were also hybridized on the Affymetrix SNP 6.0 array
2014-12-10 | E-GEOD-62407 | biostudies-arrayexpress
Project description:The International Stem Cell Initiative analyzed 127 human embryonic stem cell lines and 11 induced pluripotent cell lines, from 39 laboratories worldwide for genetic changes occurring during culture. Most cell lines were analyzed at an early and late passage. Population structure analysis from SNP detection revealed that the cell lines included representatives of all major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed but haphazardly with no link to time in culture. Structural variants (SVs), below the level of standard chromosome banding, determined from the SNP arrays, also appeared sporadically but no common variants related to culture were observed on chromosomes 1, 12 and 17. However, overlapping SV gains acquired in the chromosome 20q11.21 region during extended culture were identified in over 20% of the cell lines. Three genes within the minimal shared region, ID1, BCL2L1, and HM13, are expressed in human ES cells, with BCL2L1 a strong candidate for driving this culture adaptation of ES cells. In order to provide better insight into the frequency and types of genetic changes affecting human ES cells on prolonged passage, the ISCI has undertaken a survey by karyology and high resolution SNP array of one hundred twenty seven independent human ES cell lines, provided by thirty nine laboratories in twenty countries around the world, particularly to identify the common genetic changes that occur during prolonged culture. Here we append data from the SNP genotyping of the genomic DNA samples extracted from the human embryonic stem cells. A group of eleven human iPS cells from three laboratories was also included to provide a pilot comparison of these pluripotent cells derived by reprogramming.
2011-11-12 | E-GEOD-33522 | biostudies-arrayexpress
Project description:Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS), and leiomyosarcoma (LMS), feature myogenic differentiation. Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in nonneoplastic and benign counterparts for GIST, RMS and LMS, and the DMD deletions inactivate larger dystrophin isoforms, including 427kDa dystrophin, while preserving expression of an essential 71kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence, and invadopodia formation, and dystrophin inactivation was found in 96%, 100%, and 62% of metastatic GIST, embryonal RMS, and LMS, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in treatment of cancer. High molecular weight genomic DNA was isolated from 40 high-grade myogenic cancers (including 7 normal tissue/tumor pairs and 33 additional tumors) using QIAamp DNA Mini Kit (QIAGEN) and analyzed by Affymetrix 250K SNP array.
2014-05-02 | E-GEOD-53021 | biostudies-arrayexpress
Project description:Methods of comprehensive microarray based analyses of single cell DNA are rapidly emerging. Whole genome amplification (WGA) remains a critical component for these methods to be successful. A number of commercially available WGA kits have been independently utilized in previous single cell microarray studies. However, direct comparison of their performance on single cells has not been conducted. The present study demonstrates that among previously published methods, a single cell GenomePlex WGA protocol provides the best combination of speed and accuracy for SNP microarray based copy number analysis when compared to a REPLI-g or GenomiPhi based protocol. Alternatively, for applications that do not have constraints on turn-around time and that are directed at accurate genotyping rather than copy number assignments, a REPLI-g based protocol may provide the best solution. Affymetrix SNP arrays were processed according to the manufacturer's directions on DNA extracted from human fibroblast cell lines and single fibroblast cells. Afflymetrix SNP array analysis was successfully completed on 46 lymphocyte single cell samples, 8 gDNA extracted from cell lines, 11 reference gDNA extracted from cell lines and 3 reference gDNA samples from the RMA of New Jersey DNA bank. GSM617116 to GSM617129: CEL files were processed using GTYPE version 4 (Affymetrix Inc., Genotyping Console 4.0 Manual) using the DM algorithm for genotype calls. Copy number and loss of heterozygosity were calculated from CHP files using CNAT version 4.1 (Affymetrix Inc., Genotyping Console 4.0 Manual) analysis against a reference set consisting of three normal females from in house gDNA bank, 11 normal females from Coriel cell lines and 16 normal females from the HapMap database (www.hapmap.org). The 16 normal females are NA10855, NA10863, NA11832, NA12057, NA12234, NA12717, NA12813, NA18505, NA18508, NA18517, NA19137, NA19152, NE00088, NE00091, NE00403, and NE01119.
2010-12-20 | E-GEOD-24690 | biostudies-arrayexpress
Project description:Hypothesis: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n=50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term survivors. In squamous cell carcinoma (n=28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, mRNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic and clinical data. We identified gene copy number gains and losses, with corresponding changes in mRNA levels, that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung. Short-term (<20 months; n=53) and long-term survivors (>58 months;n=47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh-frozen tumor specimens. The samples were analyzed using high-resolution SNP-array technology. The molecular data was combined with information on clinical parameters.
2011-11-01 | E-GEOD-28572 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE28571: Gene Copy Number Aberrations are Associated with Survival in Histological Subgroups of Non-Small Cell Lung Cancer (expression data) GSE28572: Gene Copy Number Aberrations are Associated with Survival in Histological Subgroups of Non-Small Cell Lung Cancer (copy number data) Refer to individual Series
2011-11-01 | E-GEOD-28582 | biostudies-arrayexpress