Histone H3K9 methyltransferase SETDB1 overexpression correlates with pediatric high-grade gliomas progression and prognosis

Klonou, Alexia; Korkolopoulou, Penelope; Giannopoulou, Angeliki-Ioanna; Kanakoglou, Dimitrios S; Pampalou, Andromachi; Gargalionis, Antonios N.; Sarantis, Panagiotis; Mitsios, Andreas; Sgouros, Spyros; Papavassiliou, Athanasios G.; Piperi, Christina

doi:10.1007/s00109-023-02294-8

Cited by 6 publications

(1 citation statement)

References 46 publications

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“…In more detail, it acts as a bivalent tumor suppressor that inhibits GB proliferation, migration, and invasion [77]. In addition, the silencing of the oncogenic H3K9me3 methyltransferase SETDB1, which reduces cell viability and survival, appears to significantly increase SLC17A7 mRNA levels in pediatric high-grade gliomas, further confirming its tumor suppressive role [80]. SLC17A7 and glutamatergic signaling has been shown to be associated with glioma-related seizures and appears to be overexpressed in brain tissue samples of glioma patients with seizures [81].…”

Section: Slc Implication In Glioma Proliferation and Progressionmentioning

confidence: 86%

Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review

Anagnostakis,

Kokkorakis,

Markouli

et al. 2023

IJMS

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Solute carriers (SLCs) are essential for brain physiology and homeostasis due to their role in transporting necessary substances across cell membranes. There is an increasing need to further unravel their pathophysiological implications since they have been proposed to play a pivotal role in brain tumor development, progression, and the formation of the tumor microenvironment (TME) through the upregulation and downregulation of various amino acid transporters. Due to their implication in malignancy and tumor progression, SLCs are currently positioned at the center of novel pharmacological targeting strategies and drug development. In this review, we discuss the key structural and functional characteristics of the main SLC family members involved in glioma pathogenesis, along with their potential targeting options to provide new opportunities for CNS drug design and more effective glioma management.

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Section: Slc Implication In Glioma Proliferation and Progressionmentioning

confidence: 86%

Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review

Anagnostakis,

Kokkorakis,

Markouli

et al. 2023

IJMS

Self Cite

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SETDB1: Progress and prospects in cancer treatment potential and inhibitor research

Ma,

Xu,

Hou

et al. 2024

Bioorganic Chemistry

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Immunohistochemical Study of Histone Protein 3 Modification in Pediatric Osteosarcoma Identifies Reduced H3K27me3 as a Marker of Poor Treatment Response

Kondratowski,

Cohen,

Deyell

et al. 2023

Preprint

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The most common pediatric primary malignant bone tumor, osteosarcoma, is often described as genetically non-recurrent and heterogeneous. Neoadjuvant chemotherapy is typically followed by resection and assessment of treatment response, which helps inform prognosis. Identifying biomarkers that may impact chemotherapy response and survival could aid in upfront risk stratification and identify patients in highest need of innovative therapies for future clinical trials. Relative to conventional genetics, little is known about osteosarcoma epigenetics. We aimed to characterize the methylation and phosphorylation status in osteosarcoma using histone markers found in primary diagnostic biopsies and their paired metastases. We constructed two tissue microarray sets from 58 primary diagnostic samples and 54 temporally-separated but related metastatic or recurrent samples, with tissue blocks available from 2002-2022. Clinical charts were reviewed for post-therapy necrosis response, presence of metastatic disease or recurrence, and overall survival. We evaluated 6 histone H3 residues using immunohistochemistry, including H3K4me3, H3K9me3, H3K27me2, H3K27me3, H3S10T11phos, and H3S28phos. Tumors were scored with low (<25%) or high (≥25%) nuclear staining of tumor cells. Diagnostic biopsies with low H3K27me3 nuclear staining were associated with poor treatment response (≤90% necrosis) at the time of definitive excision (P<0.05). We observed loss of H3S10T11phos expression in metastatic and recurrent resections specimens compared to the primary tumor (P<0.05). Expression patterns for the remaining histone markers did not show significant associations with disease parameters or survival. Although larger cohort studies are needed, these results support the expanded evaluation of histone markers, particularly H3K27me3 and H3S10T11phos, in osteosarcoma biology and risk stratification.

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Histone H3K9 methyltransferase SETDB1 overexpression correlates with pediatric high-grade gliomas progression and prognosis

Cited by 6 publications

References 46 publications

Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review

Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review

SETDB1: Progress and prospects in cancer treatment potential and inhibitor research

Immunohistochemical Study of Histone Protein 3 Modification in Pediatric Osteosarcoma Identifies Reduced H3K27me3 as a Marker of Poor Treatment Response

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