Gene expression in laboratory models and primary tumors in Small Cell Lung Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15240 | GEO | 2009/05/26
SECONDARY ACCESSION(S): PRJNA116439
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression was measured on the Affymetrix platform in primary xenografts, xenograft-derived cell lines, secondary xenografts, normal lung, and primary tumors obtained from chemotherapy naive Small Cell Lung Cancer (SCLC). The SCLC primary xenografts were serially propagated in vivo in immunodeficient mice. Cell lines were derived from each xenograft and grown for 6 months using conventional tissue culture conditions. Secondary xenografts were obtained from cell cultures by re-implantation in immunodeficient mice. Such SCLC laboratory models were analyzed along with conventional SCLC cell lines and the derivative secondary xenografts, with normal lung and primary tumors, to assess irreversible gene expression changes induced by culturing conditions. Experiment Overall Design: SCLC primary xenografts were compared to the corresponding xenograft-derived cell lines, and to the secondary xenografts established from the cell lines using the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Gene expression from SCLC primary tumors was measured using the Affymetrix GeneChip Human Genome U133A 2.0 Array. 3 datasets: GSM380476-GSM380512, GSM380513-GSM380516, and GSM380517-GSM380520
2009-06-05 | E-GEOD-15240 | biostudies-arrayexpress
Project description:Epigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for new targeted therapies. The current report describes the discovery and biological activity of a cyclopropylamine containing inhibitor of Lysine Demethylase 1 (LSD1), GSK2879552. This small molecule is a potent, selective, orally bioavailable, mechanism-based irreversible inhibitor of LSD1. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes suggesting this may be used as a predictive biomarker of activity. The targeted mechanism coupled with a novel predictive biomarker make LSD1 inhibition an exciting potential therapy for SCLC, a highly prevalent, rarely cured, tumor type representing approximately 15% of all lung cancers. DNA methylation profiling was performed using Infinium 450K methylation arrays on SCLC cell lines, patient derived xenografts, and patient samples. Data was processed and normalized using GenomeStudio V2011.1
2015-07-14 | E-GEOD-66295 | biostudies-arrayexpress
Project description:All three transforming members of the Myc family play a significant role in the development of both SCLC and NSCLC. NSCLC constitutes 80% of all lung cancer, and cMyc expression is most often deregulated, compared with N-Myc and L-Myc, in this disease. Thus, although we are interested in understanding the regulation and function of the entire Myc family in all lung cancers, we focused our research on cMyc deregulation in NSCLC. To identify target genes whose regulatory regions are bound in response to deregulated cMyc in NSCLC, we analyzed mouse xenograft tumours established in immune-compromised mice from monolayer cell lines derived from primary adenocarcinoma NSCLCs. These xenografts were chosen for further study because they show a genetic profile similar to their respective primary tumour (MGH8, RVH6849, A549, MGH24). High c-myc expression positively correlates with the ability of NSCLC cell lines to form xenografts, suggesting that Myc contributes towards the ability of the cells to grow in vivo. We conducted Myc-specific ChIP-chip and the corresponding normal IgG control using the Agilent genome-wide oligonucleotide promoter arrays on 3 biological replicates, of each of the four xenograft tumours. Following pre-processing using variance-stabilizing normalization and statistical analysis using general linear models we identified a list of 2,207 genes significantly enriched for c-Myc binding.
2009-11-24 | GSE15002 | GEO
Project description:We investigated the gene expression changes in a library of small cell lung carcinoma (SCLC) patient-derived xenograft (PDX) models.
2022-02-07 | E-MTAB-11230 | biostudies-arrayexpress
Project description:There is a clear need to expand the toolkit of adequate mouse models and cell lines available for preclinical studies of high-grade neuroendocrine lung carcinoma (Small Cell Lung Carcinoma, SCLC and Large Cell Neuroendocrine Carcinoma, LCNEC), two highly aggressive tumor types with dismal prognosis and few therapeutic options. Actually, paucity is extreme in the case of LCNEC. Given the lack of murine cell lines and transplant models of LCNEC the need is imperative/unmet. In this study, we have generated and examined new models of LCNEC and SCLC transplantable cell lines derived from our previously developed primary mouse LCNEC and SCLC tumors. RNA-seq analysis demonstrated that our cell lines and syngeneic tumors maintained the transcriptome program from the original transgenic primary tumor, and display strong similarities to human SCLC or LCNEC. Importantly, the SCLC transplanted cell lines show the ability of metastasize, mimicking this characteristic of the human condition. In summary, we have generated mouse cell line tools that allow further basic and translational research, as well as preclinical testing of new treatment strategies for SCLC and LCNEC, as they retain important features of their human counterparts and address the lack of LCNEC disease models.
2023-10-29 | GSE242422 | GEO
Project description:In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here we explored the role of exportin 1 in NE transformation. We observed upregulated exportin 1 in lung and prostate pre-transformation adenocarcinomas. Exportin 1 was induced upregulated following genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation and extended response to targeted therapies in both lung anddifferent TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the AR inhibitor enzalutamide, and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE transformationNE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs tumors after NE transformation to standard cytotoxics. Together these data nominate exportin 1 inhibition as a novel potential therapeutic approach target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma.
2023-07-12 | GSE237072 | GEO
Project description:In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here we explored the role of exportin 1 in NE transformation. We observed upregulated exportin 1 in lung and prostate pre-transformation adenocarcinomas. Exportin 1 was induced upregulated following genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation and extended response to targeted therapies in both lung anddifferent TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the AR inhibitor enzalutamide, and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE transformationNE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs tumors after NE transformation to standard cytotoxics. Together these data nominate exportin 1 inhibition as a novel potential therapeutic approach target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma.
2023-07-12 | GSE237071 | GEO
Project description:Small cell lung cancer (SCLC) is a disease characterized by aggressive clinical behavior and lack of effective therapy. Due to its high tendency of early dissemination, only a third of patients have limited-stage disease at the time of diagnosis. SCLC is thought to derive from neuroendocrine cells of the lung. Although several molecular abnormalities in SCLC have been described, there are relatively few studies on epigenetic alterations in this type of tumor. Here, we have used methylation profiling with the methylated CpG island recovery assay (MIRA) in combination with microarrays and conducted the first genome-scale analysis of methylation changes that occur in primary SCLC and SCLC cell lines. Among hundreds of tumor-specifically methylated genes, we identified 73 gene targets that are methylated in more than 77% of primary SCLC tumors, most of which have never been linked to aberrant methylation in tumors. These targets have excellent potential for development of biomarkers for early detection of SCLC. SCLC cell lines had an ~3-fold greater number of hypermethylated genes than primary tumors. Gene ontology analysis indicated a significant enrichment of methylated genes functioning as transcription factors and in processes of neuronal differentiation. Motif analysis of tumor-specific methylated regions identified enrichment of binding sites for several neural cell fate-specifying transcription factors including NEUROD1, HAND1, ZNF423 and REST. We hypothesize that functional inactivation of their corresponding binding sites by DNA methylation can lead to an escape route for early progenitor cells towards the malignant state and may contribute to the origin of SCLC. Comparison between healthy and SCLC tumor DNA methylation profiles
2012-01-26 | E-GEOD-35341 | biostudies-arrayexpress
Project description:<p>Early passage breast cancer xenografts have been proposed as alternatives to cell lines as model systems for studying the basic biology of tumors and for advancing therapy development. This study explores the relatedness of primary disease genomes to their matched xenotransplants. Using paired-end massively parallel sequencing 17 matched progenitor tumor, xenograft and normal trios were sequenced to at least 30-fold coverage with diploid coverage of at least 95% of the genome as determined by SNP array concordance. RNA sequence was generated from the xenograft tumors. The xenografts were derived from a spectrum of tumor samples from patients with both early and advanced breast cancer.</p>
| phs000611 | dbGaP