Transcriptome analysis in medulloblastoma groups
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Tsung-Han Hsieh
PROVIDER: E-GEOD-67850 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Embryonal tumors of the central nervous system (CNS) represent a highly malignant tumor group of medulloblastoma (MB), atypical teratoid/rhabdoid tumor (AT/RT), and primitive neuroectodermal tumor (PNET) that frequently afflict children. In this study, we report transcriptome traits in MB by using gene expression microarray analyses. We also compare MB dataset with AT/RT cases and AT/RT-like cases.
2015-04-15 | GSE67850 | GEO
Project description:Pediatric embryonal brain tumor (PEBT), which includes medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), is the second most prevalent pediatric tumor type among brain tumors of childhood. AT/RT is highly malignant and is often misdiagnosed as MB and PNET. Distinguishing AT/RT from PNET/MB is of clinical significance since the survival rate of AT/RT patients is much lower. The diagnosis of AT/RT relies primarily on the morphologic assessment and immunohistochemistry (IHC) staining on a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we observed several AT/RT-like tumors, which fulfilled histopathologic and all other biomarker criteria for AT/RT diagnosis, still showed retained INI1 immunoreactivity. Recent studies also reported retained INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases. Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples for studying their genomics landscapes. AT/RT and INI(+) AT/RT-like patients had similar survival rate, and global array CGH analysis and INI1 gene sequencing showed there is no differential chromosomal aberration marker between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MB or PNET as AT/RT-like cases since transcriptome profiling revealed that not only AT/RT and INI(+) AT/RT-like cases expressed distinct mRNA and microRNA profiles, and their gene expression patterns were different from those of MBs and PNETs. AT/RTs shared the closest transcriptome profile to embryonic stem cells, INI1(+) AT/RT-like tumors were more similar to somatic neural stem cell, while MBs were closer to fetal brain. Novel biomarkers were identified to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs. Our studies disclosed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric cases. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome information unveiled in this work. 2 AT/RT-like cases and 7 AT/RT cases are subjected to transcriptome analysis.
2015-01-22 | E-GEOD-65132 | biostudies-arrayexpress
Project description:Pediatric embryonal brain tumor (PEBT), which includes medulloblastoma (MB), primitive neuroectodermal tumor (PNET) and atypical teratoid/rhabdoid tumor (AT/RT), is the second most prevalent pediatric tumor type among brain tumors of childhood. AT/RT is highly malignant and is often misdiagnosed as MB and PNET. Distinguishing AT/RT from PNET/MB is of clinical significance since the survival rate of AT/RT patients is much lower. The diagnosis of AT/RT relies primarily on the morphologic assessment and immunohistochemistry (IHC) staining on a few known markers such as the lack of INI1 protein expression. However, in our clinical practice we observed several AT/RT-like tumors, which fulfilled histopathologic and all other biomarker criteria for AT/RT diagnosis, still showed retained INI1 immunoreactivity. Recent studies also reported retained INI1 immunoreactivity among certain diagnosed AT/RTs. It is therefore necessary to re-evaluate INI1(+), AT/RT-like cases. Sanger sequencing, array CGH and mRNA microarray analyses were performed on PEBT samples for studying their genomics landscapes. AT/RT and INI(+) AT/RT-like patients had similar survival rate, and global array CGH analysis and INI1 gene sequencing showed there is no differential chromosomal aberration marker between INI1(-) AT/RT and INI(+) AT/RT-like cases. We did not misdiagnose MB or PNET as AT/RT-like cases since transcriptome profiling revealed that not only AT/RT and INI(+) AT/RT-like cases expressed distinct mRNA and microRNA profiles, and their gene expression patterns were different from those of MBs and PNETs. AT/RTs shared the closest transcriptome profile to embryonic stem cells, INI1(+) AT/RT-like tumors were more similar to somatic neural stem cell, while MBs were closer to fetal brain. Novel biomarkers were identified to distinguish INI1(-) AT/RTs, INI1(+) AT/RT-like cases and MBs. Our studies disclosed a novel INI1(+) ATRT-like subtype among Taiwanese pediatric cases. New diagnostic biomarkers, as well as new therapeutic tactics, can be developed according to the transcriptome information unveiled in this work.
2015-01-22 | GSE65132 | GEO
Project description:Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis. golub-00460 Assay Type: Gene Expression Provider: Affymetrix Array Designs: Hu6800 Organism: Homo sapiens (ncbitax) Material Types: synthetic_RNA, organism_part, whole_organism, total_RNA Disease States: synthetic_RNA, organism_part, whole_orMedulloblastoma, renal rhabdoid tumor, Atypical Teratoid/Rhabdoid Tumor, Supratentorial PNET, Supratentorial PNET (pineoblastoma), Normal, Malignant Glioma, Extrarenal Rhabdoid Tumorganism, total_RNA
2015-05-16 | E-GEOD-68956 | biostudies-arrayexpress
Project description:Primary brain tumors are classified and treated based on their histological features, however the factors which specify these tumor types remain largely unknown. We demonstrate that the over-expression of HRAS (V12) and MYC alone or in combination directs the development of glioma, CNS PNET, and atypical teratoid/rhabdoid (AT/RT)-like tumors from postnatal murine p53-deficient neural stem/progenitor cells. Microarray analyses were performed to investigate the gene expression profile of the tumor cells generated by the different genetic perturbations.
2012-03-21 | GSE28095 | GEO
Project description:Primary brain tumors are classified and treated based on their histological features, however the factors which specify these tumor types remain largely unknown. We demonstrate that the over-expression of HRAS (V12) and MYC alone or in combination directs the development of glioma, CNS PNET, and atypical teratoid/rhabdoid (AT/RT)-like tumors from postnatal murine p53-deficient neural stem/progenitor cells. Microarray analyses were performed to investigate the gene expression profile of the tumor cells generated by the different genetic perturbations. Murine brain tumors were generated by overexpressing different oncogenes in cultured neurosphere cells from the postnatal lateral ventricle wall region (LVW) of Trp53-deficient mice. Neurosphere cultures were established from isolated cells of the generated tumors, which still expressed the transgene/fluorescent marker gene cassette. Total RNA was isolated and used for gene expression analyses using the Affymetrix Gene 1.0 ST array platform.
2012-03-21 | E-GEOD-28095 | biostudies-arrayexpress
Project description:Human medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
2015-12-11 | GSE68627 | GEO
Project description:Atypical teratoid/rhabdoid tumor (AT/RT), which harbors INI1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatments. Here we established human INI1-deficient pluripotent stem cells (hPSCs), which developed AT/RT formation in vivo. However, INI1-deficient hPSC-derived neural progenitor cell (NPC) gave rise to mostly medulloblastoma-like tumors when transplanted into the mouse brain.
2019-06-20 | GSE118653 | GEO
Project description:Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive CNS-tumors of infancy and early childhood. Hallmark is the surprisingly simple genomics with a truncating mutation in the SMARCB1 gene as the oncogenic driver. Nevertheless, AT/RTs are infiltrated by immune cells and even clonally expanded T-cells. However, it is unclear, what T-cells might recognize on AT/RT cells. Here, we report a comprehensive analysis of naturally presented HLA-class-I and class-II ligands on n=23 AT/RTs. MS-based analysis of the HLA-ligandome revealed 55 class-I and 139 class-II peptides from tumor-associated proteins.
2022-05-31 | PXD033935 | Pride
Project description:Atypical teratoid/rhabdoid tumor (AT/RT), which harbors INI1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatments. Here we established human INI1-deficient pluripotent stem cells (hPSCs), which developed AT/RT formation in vivo. We revealed that the activation of ESC-like signature leads to rhabdoid phenotype in tumor by OSKM or c-MYC induction. Finally, we performed CRISPR/Cas9 knockout screening to inhibit activation of ESC-like signature in AT/RT. Our effort identified candidate genes including RAD21 that encodes a key component within the cohesin complex. Notably, chemical inhibition of HDAC8 that indirectly targets the function of cohesin with simultaneous inhibition of EZH2 efficiently suppressed the activation of ESC-like signature and inhibited the growth of AT/RT cells both in vitro and in vivo.
2019-06-20 | GSE118654 | GEO