Genomics

Dataset Information

38

Affymetrix SNP array data for NSCLC samples


ABSTRACT: Non-small cell lung cancer (NSCLC) presents a notoriously genomically unstable cancer type, with numerous large scale and focal genomic aberrations resulting in gene copy number variations across the whole genome. The relations of these gene copy number changes to subsequent mRNA levels are only fragmentarily understood. The aim of this study was an integrated analysis of gene copy number changes and corresponding gene expression in a large clinically annotated NSCLC patient cohort. Fresh frozen tumor sample from 190 resected NSCLC patients were subjected to SNP arrays and gene expression array analysis resulting 39788 tested copy number/ RNA expression pairs. Correlation analysis using an externally centered correlation coefficient (ECCC) revealed that gene expression of 19058 genes was significantly influenced by gene copy number changes (FDR < 0.05). However, only 440 probe sets demonstrated high correlations (ECCC > 0.7) that were mostly due to few cases with high gene copy number gains. These gene copy number dependent genes were clustered in only few chromosomal hot spot regions and classical oncogenes (e.g. EGFR, MDM2, KRAS) are overrepresented among these genes. In a meta-analysis, including 1585 NSCLC patients, gene expression levels from 70 of 440 (16%) gene-copy-number-dependent genes were associated with survival. In conclusion, the genome-wide analysis indicates that gene copy number aberrations influence directly gene expression levels in a distinct subset of genes. The concrete illustration of these molecular relations help to interpret the impact of gene copy number changes and may serve as starting points to identify new cancer drivers in NSCLC. Overall design: Affymetrix Gene Chip Human Mapping 250K Nsp I arrays wer performed according to the manufacturer's directions with genomic DNA extracted from fresh frozen lung cancer tissue. Copy number analysis of Affymetrix 250 K arrays was performed on DNA from 190 NSCLC patients. These data sets belongs to the previous described cohort of 100 cases (Micke et al. 2011, GSE28582). Thus altogether the cohort used in the comprehensive gene copy number analysis comprised 190 patients.

REANALYSIS of: GSE28582

INSTRUMENT(S): [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array

SUBMITTER: Patrick Micke  

PROVIDER: GSE76730 | GEO | 2016-08-31

SECONDARY ACCESSION(S): PRJNA308490

REPOSITORIES: GEO

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Publications

Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer.

Micke Patrick P   Edlund Karolina K   Holmberg Lars L   Kultima Hanna Göransson HG   Mansouri Larry L   Ekman Simon S   Bergqvist Michael M   Scheibenflug Lena L   Lamberg Kristina K   Myrdal Gunnar G   Berglund Anders A   Andersson Annsofie A   Lambe Mats M   Nyberg Fredrik F   Thomas Andrew A   Isaksson Anders A   Botling Johan J  

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20111101 11


<h4>Introduction</h4>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.<h4>Methods</h4>Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a cl  ...[more]

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