BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology

Shankar, Ganesh M.; Lelic, Nina; Gill, Corey M.; Thorner, Aaron R.; Hummelen, Paul Van; Wisoff, Jeffrey H.; Loeffler, Jay S.; Brastianos, Priscilla K.; Shin, John H.; Borges, Lawrence F.; Butler, William E.; Zagzag, David; Brody, Rachel; Duhaime, Ann‐Christine; Taylor, Michael D.; Hawkins, Cynthia; Louis, David N.; Cahill, Daniel P.; Curry, William T.; Meyerson, Matthew

doi:10.1007/s00401-015-1492-2

Cited by 58 publications

(56 citation statements)

References 21 publications

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“…However, a surge in DIPG research in recent years may prove to turn the tide. Comprehensive genomic studies identified the oncohistone H3K27M as the hallmark of pediatric gliomas affecting the midline of the central nervous system (Wu et al 2012; Schwartzentruber et al 2012; Khuong-Quang et al 2012; Gessi et al 2015; Shankar et al 2016). Central to DIPG oncogenesis (Funato et al 2014), the presence of H3K27M mutant histones alters the function of the PRC2 complex responsible for H3K27 trimethylation (Lewis et al 2013) and results in broad dysregulation of transcription (Chan et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma

et al. 2017

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Summary Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. Identification of super-enhancers in DIPG provides insights toward the cell of origin, highlighting oligodendroglial lineage genes, and reveals unexpected mechanisms mediating tumor viability and invasion, including potassium channel function and EPH receptor signaling. The findings presented demonstrate transcriptional vulnerabilities and elucidate previously unknown mechanisms of DIPG pathobiology.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma

et al. 2017

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“…Although several studies have been published, no information has been provided with regard to patient age or WHO grade [5]; a total 18 cases including the present two cases have involved the investigation of the H3F3A gene in adult (C20 years of age) cases of HGG [3,9]. Of these, 11 cases (61 %) exhibited H3F3A K27 M mutations.…”

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confidence: 99%

Genetic mutations in high grade gliomas of the adult spinal cord

et al. 2016

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“…All of the reported spinal cord gliomas harboring BRAF V600E mutations are LGGs (Table ) . Among the 24 cases of spinal cord HGGs investigated, none of them harbored BRAF V600E mutation (Table ) . Hence, our case is the first report of a spinal cord HGG harboring BRAF V600E mutation.…”

Section: Discussionmentioning

confidence: 74%

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

et al. 2020

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A 17‐year‐old female complained of lower extremity pain that progressed to low back pain accompanied by paraparesis. Magnetic resonance imaging revealed a mass in the conus medullaris of the spinal cord at the thoracic spine 11–12 level. The patient underwent resection of the mass. The pathological diagnosis was anaplastic astrocytoma based on the densely proliferating astrocytic tumor cells without necrosis or microvascular proliferation. The patient received chemoradiotherapy with oral temozolomide and a total of 54 Gy of local irradiation, followed by 24 courses of temozolomide as maintenance chemotherapy. The patient survived for 8 years without tumor recurrence following the initial treatment. Genetic analysis of the tumor revealed a BRAF V600E mutation that has not yet been reported in spinal cord high‐grade gliomas (HGGs). In recent years, the molecular therapy targeting the BRAF V600E mutation has been applied in clinical practice for several cancer types. Although the frequency in spinal cord HGGs is uncertain, it is necessary to investigate BRAF V600E mutation as a potential therapeutic target in the future.

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BRAF alteration status and the histone H3F3A gene K27M mutation segregate spinal cord astrocytoma histology

Cited by 58 publications

References 21 publications

Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma

Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma

Genetic mutations in high grade gliomas of the adult spinal cord

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

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