Project description:Expression profiling according to differentiation was analysed in 34 neuroblastomas Experiment Overall Design: Unsupervised clusterings were performed to confirm the link between phenotype of differentiation and expression profile Experiment Overall Design: Different groups were compared with SAM-t tests.
Project description:Genome wide DNA methylation profiling of primary neuroblastomas. The Illumina 450k methylation array was used to obtain DNA methylation profiles across approximately 485,000 CpGs in 58 neuroblastomas. Data were analyzed with regard to differential methylation at ATRX and DAXX loci in relation to genomic MYCN, TERT and ATRX status, presence of alternative lengthening of telomeres (ALT) and TERT expression. The analysis is part of the study: A mechanistic classification of clinical phenotypes in neuroblastoma (Ackermann et al., 2018)
Project description:To confirm the neuroblastomas (NB) identity of human neuroblastomas from mouse-human neural crest chimeric mice model (CHNBs) we characterized their gene expression profiles by RNA-Seq (CHNBs MYCN+ALKF1174L; n=8). For a global comparison of gene expression profiles of CHNBs with other NB models, we further collected RNA-seq data from patient derived xenografts of neuroblastoma (PDX NBs ; MYCNamp+ALKwt PDX; n=2, and MYCNamp+ALKF1174L PDX; n=3), neuroblastomas from genetically engineered mouse model (GEMM NBs; Th-MYCN+ALKF1174L; n=3), neuroblastoma established cell lines (n=2; Kelly, MYCNamp+ALKF1174L; SH-SY5Y, MYCNwt+ ALKF1174L), human pluripotent derived human neural crest cells (hNCCs; wt hNCCs; n=2, and MYCN+ALKF1174L hNCCs, with Dox; n=2) and from hNCC xenografts (MYCN+ALKF1174L; n=5).
Project description:Reference1: Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, Nakagawa A, Hirata T, Kubo H, Goto T, Yamada S, Yoshida Y, Fuchioka M, Ishii S, Nakagawara A. Expression profiling of human primary Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas. Cancer Cell. 2005 Apr;7(4):337-50. To predict the prognosis of neuroblastoma patients and choose a better therapeutic protocol, we developed a cDNA microarray carrying 5340 genes obtained from primary neuroblastomas and examined 136 tumor samples. We made a probabilistic output statistical classifier that provided a high accuracy in prognosis prediction (89% at 5 years) and a highly reliable method to validate it. Kaplan-Meier analysis indicated that the patients in an intermediate group defined by existing markers are divided by microarray into two further groups with 5 year survivals for 36% and 89% of patients (p < 10(-4)), i.e., with unfavorably and favorably predicted neuroblastomas, respectively. According to these results, we developed a gene subset chip for a clinical tool, for which our classifier exhibited 88% prediction accuracy. Datasets: neuroblastomas by CCC-NB200-Chip: GSM42338-GSM42387 Expression profiling of human primary neuroblastomas by CCC-NB5000-Chip: GSM42391-GSM42526 Keywords = Neuroblastoma Keywords: other
Project description:Amplification of MYCN is the most prominent genetic marker of high-stage neuroblastoma, a childhood tumor originating from the neural crest. We generated a transgenic mouse with Cre-conditional induction of MYCN in dopamine beta hydroxylase expressing cells that develops murine neuroblastomas.
Project description:SNP arrays were combined with next generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma aetiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in vivo models.
Project description:SNP arrays were combined with next generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma aetiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in vivo models.
Project description:Reference1: Ohira M, Oba S, Nakamura Y, Isogai E, Kaneko S, Nakagawa A, Hirata T, Kubo H, Goto T, Yamada S, Yoshida Y, Fuchioka M, Ishii S, Nakagawara A. Expression profiling of human primary Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas. Cancer Cell. 2005 Apr;7(4):337-50. To predict the prognosis of neuroblastoma patients and choose a better therapeutic protocol, we developed a cDNA microarray carrying 5340 genes obtained from primary neuroblastomas and examined 136 tumor samples. We made a probabilistic output statistical classifier that provided a high accuracy in prognosis prediction (89% at 5 years) and a highly reliable method to validate it. Kaplan-Meier analysis indicated that the patients in an intermediate group defined by existing markers are divided by microarray into two further groups with 5 year survivals for 36% and 89% of patients (p < 10(-4)), i.e., with unfavorably and favorably predicted neuroblastomas, respectively. According to these results, we developed a gene subset chip for a clinical tool, for which our classifier exhibited 88% prediction accuracy. Datasets: neuroblastomas by CCC-NB200-Chip: GSM42338-GSM42387 Expression profiling of human primary neuroblastomas by CCC-NB5000-Chip: GSM42391-GSM42526 Keywords = Neuroblastoma