Project description:Primary tumor recurrence occurs commonly after surgical resection of lung squamous cell carcinoma (SCC). The aim of this study was to identify genes involved in recurrence in lung squamous cell carcinoma patients. Array comparative genomic hybridization (aCGH) was performed on DNA extracted from tumour tissue from 62 patients with primary lung squamous cell carcinomas. aCGH data was analysed to identify genes affected by copy number alterations that may be involved in SCC recurrence. Candidate genes were then selected for technical validation based on differential copy number between recurrence and non-recurrence SCC tumour samples. Genes technically validated advanced to tests of biological replication by qPCR using an independent test set of 72 primary lung SCC tumour samples. 18q22.3 loss was identified by aCGH as significantly associated with recurrence (p=0.038). Although aCGH copy number loss associated with recurrence was found for seven genes within 18q22.3, only SOCS6 copy number loss was both technically replicated by qPCR and biologically validated in the test set. DNA copy number profiling using 44K element array comparative genomic hybridization microarrays of 62 primary lung squamous cell carcinomas.
Project description:Primary tumor recurrence occurs commonly after surgical resection of lung squamous cell carcinoma (SCC). The aim of this study was to identify genes involved in recurrence in lung squamous cell carcinoma patients. Array comparative genomic hybridization (aCGH) was performed on DNA extracted from tumour tissue from 62 patients with primary lung squamous cell carcinomas. aCGH data was analysed to identify genes affected by copy number alterations that may be involved in SCC recurrence. Candidate genes were then selected for technical validation based on differential copy number between recurrence and non-recurrence SCC tumour samples. Genes technically validated advanced to tests of biological replication by qPCR using an independent test set of 72 primary lung SCC tumour samples. 18q22.3 loss was identified by aCGH as significantly associated with recurrence (p=0.038). Although aCGH copy number loss associated with recurrence was found for seven genes within 18q22.3, only SOCS6 copy number loss was both technically replicated by qPCR and biologically validated in the test set.
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.
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.
Project description:The basaloid carcinoma (pure) and the (mixed) basalod variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient. In order to assess their molecular specificity among other lung squamous cell carcinomas we analysed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCC, including 42 basaloid samples (24 pure, 18 mixed).
Project description:Genomic profiling of human squamous cell carcinoma cell lines cells and corresponding primary tumors Descriptive experiment, studying DNA copy number alterations in 6 newly established human squamous cell carcinoma cell lines cells and corresponding 6 primary tumors.
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.
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 array-based gene expression profiling. The molecular data was combined with information on clinical parameters.