Transcriptomics,Genomics

Dataset Information

38

HOXA5 is a survival locus associated with chromosome 7 gain in IDH-wildtype glioblastoma


ABSTRACT: Glioblastomas (GBMs) are divided into CpG Island Methylator Phenotype (CIMP) and non-CIMP tumors. Non-CIMP GBMs derive from cells with non-disjunction of chromosome (chr7) and chromosome 10 (chr10), resulting in chr7 gain and chr10 loss, while CIMP GBMs have mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2). Gain of chr7 is largely driven by PDGFA, but other genes on chr7 are likely to contribute to fitness gains and aggressiveness of these GBMs. We computationally investigated genes on chr7 whose gene expression correlated with survival, identifying HOXA5 as a potential driver of proneural gliomagenesis. Using a combination of human GBM cells and mouse PDGF-driven gliomas, we showed that HOXA5 drives increased proliferation and radiation resistance in culture and in vivo. These phenotypes appear to be in part due to effects on p53 and other apoptosis-related genes. Overall design: In order to determine whether elevated HOXA5 gene expression is causally related to aggressiveness of non-CIMP PN GBM, we used a PDGF-driven PN GBM mouse model based on the RCAS/tva system to perform gain of function analysis for HOXA5.

INSTRUMENT(S): Illumina MouseWG-6 v2.0 expression beadchip

SUBMITTER: Sonali Arora  

PROVIDER: GSE89409 | GEO | 2018-04-09

REPOSITORIES: GEO

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Publications

Increased HOXA5 expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma.

Cimino Patrick J PJ   Kim Youngmi Y   Wu Hua-Jun HJ   Alexander Jes J   Wirsching Hans-Georg HG   Szulzewsky Frank F   Pitter Ken K   Ozawa Tatsuya T   Wang Jiguang J   Vazquez Julio J   Arora Sonali S   Rabadan Raul R   Levine Ross R   Michor Franziska F   Holland Eric C EC  

Genes & development 20180409 7-8


Glioblastoma is the most frequently occurring and invariably fatal primary brain tumor in adults. The vast majority of glioblastomas is characterized by chromosomal copy number alterations, including gain of whole chromosome 7 and loss of whole chromosome 10. Gain of whole chromosome 7 is an early event in gliomagenesis that occurs in proneural-like precursor cells, which give rise to all isocitrate dehydrogenase (IDH) wild-type glioblastoma transcriptional subtypes. Platelet-derived growth fact  ...[more]

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