Genomic Analysis of Pediatric low-grade gliomas
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ABSTRACT:
PROVIDER: PRJNA198059 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We carried out the analyses of chromosome variations between low-grade and high-grade gliomas in Chinese population. We found out the differences in chromosomes, cytobands, genes, pathways and GO functions. To identify the glioma tissue-specific genomic alterations and compare the genomic variations between low-grade and high-grade gliomas.
2015-01-03 | E-GEOD-34888 | biostudies-arrayexpress
Project description:Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but apart from BRAF mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. These tumors are particularly poorly understood. We performed high-resolution copy-number analysis of 44 diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gains, were observed in 28% of diffuse astrocytomas grade II (DA2s) and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene MYB on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged DA2 demonstrated MYBL1 tandem duplication, and few other events. Two novel, truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth when expressed in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas.
2013-04-23 | GSE45843 | GEO
Project description:We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, histological subtypes as well as BRAF genetic status We also compared molecular differences to normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain expression. We analyzed the expression of 6,100 genes among 151 FFPE pediatric and 15 FFPE adult low-grade gliomas and analyzed how the expression patterns changes with location, age, histology and BRAF genomic status and how those differences were mirrored in normal brain expression. The values in the sample 'characteristics' columns represent; Location; SUP= Supratentorial, INF= Infratentorial Histology; PA= pilocytic astrocytoma, GG= ganglioglioma, DNT= dysembryoplastic neuroepithelial tumor, OD= oligodendroglial tumors, NOS= not otherwise specified tumors BRAF status; DUP= BRAF duplication, MUT= BRAF V600E mutation, WT= wild type, ND= not determined Primary or recurrent tumor; P=primary, R=recurrent Primary tumor that further progressed; 1=yes, 0=no, _=recurrent tumors only
2014-08-29 | E-GEOD-60898 | biostudies-arrayexpress
Project description:Alterations in Fibroblast growth factor receptor proteins frequently occur as oncogenes in many cancers. FGFR alterations have been reported in a subset of pediatric gliomas, representing a therapeutic target for precision medicine approaches. We performed a genomic analysis of 13,659 gliomas and found that 4.5% harbor FGFR alterations including structural variants and single nucleotide variants. FGFR family members are differentially enriched by age, tumor grade, and histological subtype. FGFR1 alterations are most frequent in pediatric gliomas, particularly pediatric low-grade gliomas, while FGFR3 drivers were associated with adult gliomas. In vitro and in vivo functional studies confirm FGFR1 alterations to be sufficient to activate MAPK and mTOR signaling, drive gliomagenesis and activate neuronal transcriptional programs. FGFR1-driven models showed sensitivity to MAPK pathway inhibitors, including panFGFR inhibitors that are FDA approved for use in other cancers. While early FGFR inhibition was sufficient to prolong survival of mice bearing FGFR-driven xenografts, this was insufficient to induce cures. Similarly, review of patients treated with currently available MAPK pathway or FGFR inhibitors revealed modest responses. This study provides key insights into the biology of FGFR1-altered gliomas and potential strategies to therapeutically target them.
2025-05-16 | GSE273990 | GEO
Project description:Alterations in Fibroblast growth factor receptor proteins frequently occur as oncogenes in many cancers. FGFR alterations have been reported in a subset of pediatric gliomas, representing a therapeutic target for precision medicine approaches. We performed a genomic analysis of 13,659 gliomas and found that 4.5% harbor FGFR alterations including structural variants and single nucleotide variants. FGFR family members are differentially enriched by age, tumor grade, and histological subtype. FGFR1 alterations are most frequent in pediatric gliomas, particularly pediatric low-grade gliomas, while FGFR3 drivers were associated with adult gliomas. In vitro and in vivo functional studies confirm FGFR1 alterations to be sufficient to activate MAPK and mTOR signaling, drive gliomagenesis and activate neuronal transcriptional programs. FGFR1-driven models showed sensitivity to MAPK pathway inhibitors, including panFGFR inhibitors that are FDA approved for use in other cancers. While early FGFR inhibition was sufficient to prolong survival of mice bearing FGFR-driven xenografts, this was insufficient to induce cures. Similarly, review of patients treated with currently available MAPK pathway or FGFR inhibitors revealed modest responses. This study provides key insights into the biology of FGFR1-altered gliomas and potential strategies to therapeutically target them.
2025-05-16 | GSE273989 | GEO
Project description:<p>Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from mutations or duplications in the BRAF kinase in specific subclasses, few genetic driver events are known. Diffuse PLGGs compose a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. These tumors are particularly poorly understood. We performed high-resolution copy-number analysis of 44 diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gains, was observed in 28% of diffuse astrocytoma WHO grade II (DA2) and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene MYB on 6q23.3. Whole genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Two truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth when expressed in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. "Reprinted from www.pnas.org/cgi/doi/10.1073/pnas.1300252110 with permission from PNAS." </p>
| phs000614 | dbGaP
Project description:Low grade gliomas subtype analysis
| PRJEB9786 | ENA
Project description:Alterations in Fibroblast growth factor receptor proteins frequently occur as oncogenes in many cancers. FGFR alterations have been reported in a subset of pediatric gliomas, representing a therapeutic target for precision medicine approaches. We performed a genomic analysis of 13,659 gliomas and found that 4.5% harbor FGFR alterations including structural variants and single nucleotide variants. FGFR family members are differentially enriched by age, tumor grade, and histological subtype. FGFR1 alterations are most frequent in pediatric gliomas, particularly pediatric low-grade gliomas, while FGFR3 drivers were associated with adult gliomas. In vitro and in vivo functional studies confirm FGFR1 alterations to be sufficient to activate MAPK and mTOR signaling, drive gliomagenesis and activate neuronal transcriptional programs. FGFR1-driven models showed sensitivity to MAPK pathway inhibitors, including panFGFR inhibitors that are FDA approved for use in other cancers. While early FGFR inhibition was sufficient to prolong survival of mice bearing FGFR-driven xenografts, this was insufficient to induce cures. Similarly, review of patients treated with currently available MAPK pathway or FGFR inhibitors revealed modest responses. This study provides key insights into the biology of FGFR1-altered gliomas and potential strategies to therapeutically target them.
2025-05-16 | GSE286565 | GEO
Project description:<p>Pediatric low-grade gliomas (PLGGs) are the most common pediatric brain-tumor, with more than ten histologic subtypes recognized by the World Health Organization. We performed a genomic analysis of 230 PLGGs of which 73 had whole genome/RNA sequencing performed and show that MYB-QKI fusions define the seizure associated tumor, Angiocentric Glioma (AG). MYB-QKI fusions present in AGs contribute to tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of QKI, a tumor suppressor gene. Such interplay between three oncogenic mechanisms has diagnostic and therapeutic implications in AGs, and illustrates the functional complexity associated with rearrangements in cancer. </p>
| phs001054 | dbGaP
Project description:Categorisation of LGGs related to their lesion site (infratentorial vs. supratentorial) 40 Low grade gliomas samples
2013-09-21 | E-GEOD-28238 | biostudies-arrayexpress