0000000000143260

AUTHOR

Barbara Hero

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction

Background Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. Results We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being …

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Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients.

Abstract Background Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations. Methods In an international collaboration, normalized high-resolution DNA copy number data (arrayCGH and SNP arrays) from 556 high-risk neuroblastomas obtained at diagnosis were coll…

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Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.

Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review su…

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Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma: a report from the International Neuroblastoma Risk Group Project.

Abstract Purpose Increasing age has been an adverse risk factor in children with neuroblastoma (NB) since the 1970’s, with a 12-month age-at-diagnosis cut-off for treatment stratification. Over the last 30 years, treatment intensity for children >12 months with advanced-stage disease has increased; to investigate if this strategy has improved outcome and/or reduced the prognostic influence of age, we analysed the International Neuroblastoma Risk Group (INRG) database. Patients and methods Data from 11,037 children with NB (1974–2002) from Australia, Europe, Japan, North America. Cox modelling of event-free survival (EFS) tested if the era and prognostic significance of age-of-diagnosis, adj…

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Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers.

Abstract Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression–based classification and established prognostic markers. Experimental Design: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4 × 44 K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n = 634) by Kaplan–Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity, 0.93; specificity, 0.97) in the validation coh…

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Risk estimation in localized unresectable single copy MYCN neuroblastoma by the status of chromosomes 1p and 11q

In localized neuroblastoma, the identification of patients requiring intensive treatment is still difficult. We retrospectively analyzed data of 280 single copy MYCN stage 2 and 3 neuroblastoma patients with gross residual tumor after initial surgery. The 3-year-event free survival of the total group was 83+/-2%, and 3-year-overall survival was 92+/-2%. Patients < or=1.5 years had a better outcome than older children. Deletions/imbalances of chromosome 1p were found in 9/90 patients and were associated with a higher event rate but not with a higher death rate. Aberrations of chromosome 11q in 14/91 patients were correlated with a higher event and death rate. Multivariate analysis identified…

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