Loss of Heterozygosity and Copy Number Abnormality in Clear Cell Renal Cell Carcinoma Discovered by High-Density Affymetrix 10K Single Nucleotide Polymorphism Mapping Array1

Genetic aberrations are crucial in renal tumor progression. In this study, we describe loss of heterozygosity (LOH) and DNA-copy number abnormalities in clear cell renal cell carcinoma (cc-RCC) discovered by genome-wide single nucleotide polymorphism (SNP) arrays. Genomic DNA from tumor and normal tissue of 22 human cc-RCCs was analyzed on the Affymetrix GeneChip Human Mapping 10K Array. The array data were validated by quantitative polymerase chain reaction and immunohistochemistry. Reduced DNA copy numbers were detected on chromosomal arm 3p in 91%, on chromosome 9 in 32%, and on chromosomal arm 14q in 36% of the tumors. Gains were detected on chromosomal arm 5q in 45% and on chromosome 7 in 32% of the tumors. Copy number abnormalities were found not only in FHIT and VHL loci, known to be involved in renal carcinogenesis, but also in regions containing putative new tumor suppressor genes or oncogenes. In addition, microdeletions were detected on chromosomes 1 and 6 in genes with unknown impact on renal carcinogenesis. In validation experiments, abnormal protein expression of FOXP1 (on 3p) was found in 90% of tumors (concordance with SNP array data in 85%). As assessed by quantitative polymerase chain reaction, PARK2 and PACRG were down-regulated in 57% and 100%, respectively, and CSF1R was up-regulated in 69% of the cc-RCC cases (concordance with SNP array data in 57%, 33%, and 38%). Genome-wide SNP array analysis not only confirmed previously described large chromosomal aberrations but also detected novel microdeletions in genes potentially involved in tumor genesis of cc-RCC

Comparison of GeneChip, nCounter, and Real-Time PCR–Based Gene Expressions Predicting Locoregional Tumor Control after Primary and Postoperative Radiochemotherapy in Head and Neck Squamous Cell Carcinoma

This article compares the expression and applicability of biomarkers, from single genes and gene signatures, identified in patients with locally advanced head and neck squamous cell carcinoma using the GeneChip Human Transcriptome Array 2.0, nCounter, and real-time PCR analyses. Two multicenter, retrospective cohorts of patients with head and neck squamous cell carcinoma from the German Cancer Consortium Radiation Oncology Group who received postoperative radiochemotherapy or primary radiochemotherapy were considered. Real-time PCR was performed for a limited number of 38 genes of the cohort who received postoperative radiochemotherapy only. Correlations between the methods were evaluated by the Spearman rank correlation coefficient. Patients were stratified based on the expression of putative cancer stem cell markers, hypoxia-associated gene signatures, and a previously developed seven-gene signature. Locoregional tumor control was compared between these patient subgroups using log-rank tests. Gene expressions obtained from nCounter analyses were moderately correlated to GeneChip analyses (median ρ = approximately 0.68). A higher correlation was obtained between nCounter analyses and real-time PCR (median ρ = 0.84). Significant associations with locoregional tumor control were observed for most of the considered biomarkers evaluated by GeneChip and nCounter analyses. In general, all applied biomarkers (single genes and gene signatures) classified approximately 70% to 85% of the patients similarly. Overall, gene signatures seem to be more robust and had a better transferability among different measurement methods

A novel 2-metagene signature to identify high-risk HNSCC patients amongst those who are clinically at intermediate risk and are treated with PORT.

(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco-regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco-regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy