Squamous cell carcinoma (SCC) of lung is a devastating malignancy with no effective treatments, due to its complex genomic profile. Therefore, pre-clinical models mimicking its salient features are urgently needed. Here we describe mouse models bearing various combinations of genetic lesions predominantly found in human SCC. We show that Sox2 but not Fgfr1 overexpression in tracheobronchial basal cells combined with Cdkn2ab and Pten loss results in SCC closely resembling the human counterpart. Interestingly, Sox2;Pten;Cdkn2ab mice develop SCC with a more peripheral location when Club or Alveolar type 2 (AT2) cells are targeted. Our model highlights the essential role of Sox2 in promoting a squamous cell fate from different cells-of-origin and represents an invaluable tool for the developing better intervention strategies. Overall design: After RNA extraction and Bioanalyzer analysis, we processed samples with high quality RNA profiles using Illumina Hiseq2500.
SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin.
Specimen part, Disease, Disease stage, Subject
View SamplesThe cerebral cortex underwent a rapid expansion and complexification during recent primate evolution, but the underlying developmental mechanisms remain essentially unknown.
Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.
Specimen part
View SamplesHypothesis: 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.
Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.
Specimen part
View SamplesThe delicate interaction between cancer cells and the surrounding stroma plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer.
CD99 is a novel prognostic stromal marker in non-small cell lung cancer.
Specimen part, Subject
View SamplesAnalysis of HeLa cells following depletion of BRCA1 tumor supressor using RNAi against BRCA1. Results provide insight into the molecular mechanisms underlying loss of the BRCA1 function.
BRCA1 represses amphiregulin gene expression.
Treatment
View SamplesSmall Cell Lung Cancer (SCLC) is the most aggressive type of lung cancer with early metastatic dissemination and invariable development of resistant disease for which no effective treatment is available to date. Mouse models of SCLC based on inactivation of Rb1 and Trp53 developed earlier showed frequent amplifications of two transcription factor genes: Nfib and Mycl. Overexpression of Nfib but not Mycl in SCLC mouse results in an enhanced and altered metastatic profile, and appears to be associated with genomic instability. NFIB promotes tumor heterogeneity with the concomitant expansive growth of poorly differentiated, highly proliferative, and invasive tumor cell populations. Consistent with the mouse data, NFIB expression in high-grade human neuroendocrine carcinomas correlates with advanced stage III/IV disease warranting its further assessment as a potentially valuable progression marker in a clinical setting. Overall design: Genomic DNA from mouse small cell lung tumor samples was analyzed by mate pair sequencing and low coverage sequencing. And RNA from Nfib overexpressing mouse small cell lung cancer cell lines was further analyzed for high quality RNA profiles using Illumina Hiseq2500. This series contains only RNA-seq data.
Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients.
Specimen part, Subject
View SamplesNext-generation sequencing (NGS) technology applications like RNA-sequencing (RNA-seq) have dramatically expanded the potential for novel genomics discoveries, but the proliferation of various platforms and protocols for RNA-seq has created a need for reference data sets to help gauge the performance characteristics of these disparate methods. Here we describe the results of the ABRF-NGS Study on RNA-seq, which leverages replicate experiments across multiple sites using two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS). These results show high (R2 >0.9) intra-platform consistency across test sites, high inter-platform concordance (R2 >0.8) for transcriptome profiling, and a large set of novel splice junctions observed across all platforms. Also, we observe that protocols using ribosomal RNA depletion can both salvage degraded RNA samples and also be readily compared to polyA-enriched fractions. These data provide a broad foundation for standardization, evaluation and improvement of RNA-seq methods. Overall design: Two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS). Please note that the samples were named following the ABRF-Platform-Site-Sample-Replicate# format. For example, ABRF-454-CNL-A-1 means Sample A was run on 454 platform at Cornell and this is the first replicate, and ABRF-454-CNL-A-2 means the same exact sample was ran with same machine at same location and is 2nd replicate.
RNA-seq of human reference RNA samples using a thermostable group II intron reverse transcriptase.
Specimen part, Subject
View SamplesSaturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA).
Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes.
Specimen part
View SamplesWhole blood (paxgene) gene expression was measured using Affymetrix microarray from 377 individuals with rheumatoid arthritis.
Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.
Sex, Age, Specimen part, Disease
View Samples