Gliomas arising in the setting of Li-Fraumeni syndrome stratify into two molecular subgroups with divergent clinicopathologic features

Sloan, Emily A.; Hilz, Stephanie; Gupta, Rohit; Cadwell, Cathryn R.; Ramani, Biswarathan; Hofmann, J; Kline, Cassie; Banerjee, Anu; Reddy, Alyssa; Bush, Nancy Ann Oberheim; Chang, Susan M.; Braunstein, Steve; Chang, Edward F.; Raffel, Corey; Gupta, Nalin; Sun, Peter; Kim, John Y.H.; Moes, Gregory; Alva, Elizabeth; Li, Rong; Bruggers, Carol S.; Alashari, Mouied; Wetmore, Cynthia; Garg, Shipra; Dishop, Megan K.; Ziffle, Jessica Van; Onodera, Courtney; Devine, Patrick; Grenert, James P.; Lee, Julieann C.; Pekmezci, Melike; Tihan, Tarık; Bollen, Andrew W.; Berger, Mitchel S.; Costello, J; Perry, Arie; Solomon, David A.

doi:10.1007/s00401-020-02144-8

Cited by 22 publications

(16 citation statements)

References 13 publications

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“…In particular, such patients frequently develop choroid plexus carcinomas, SHH medulloblastomas, or IDH-mutated astrocytomas (for a review see [ 1 ]). IDH wild type glioblastomas have recently been observed in three LFS patients [ 2 ]. However, due to the small number of described cases, both the frequency and the molecular spectrum of such glioblastomas remain less clear.…”

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confidence: 99%

“…Similarly, few reports point to a rather high frequency of TP53 mutations in malignant pediatric glioma with MYCN amplification [ 5 ], but the risk of TP53 constitutional mutations has never been assessed. On the other hand, two cases of IDH wild type gliomas in LFS patients have only recently been described to harbor MYCN amplifications [ 2 ]. Together, the here presented cases expand the spectrum of brain tumors occurring in patients with LFS.…”

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confidence: 99%

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Malignant gliomas with H3F3A G34R mutation or MYCN amplification in pediatric patients with Li Fraumeni syndrome

et al. 2021

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Malignant gliomas with H3F3A G34R mutation or MYCN amplification in pediatric patients with Li Fraumeni syndrome

et al. 2021

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“…A total of six cases of pediatric patients with LFS and brain HGGs were identified ( Table 1 ). Among these, four were described by Sloan and colleagues [ 2 ], who performed a comprehensive genomic characterization and studied the clinicopathologic features. García-Cárdenas et al [ 3 ] reported a case of an Ecuadorian pediatric patient with anaplastic astrocytoma genetically characterized using a panel-based next-generation sequencing, whereas Zureick et al [ 4 ] reported the case of a 14-year-old boy with LFS and a gigantocellular-type glioblastoma multiforme successfully treated with surgical resection, radiotherapy and Everolimus administration.…”

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confidence: 99%

A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Messina

Cazzato

Perillo

et al. 2021

Neurology International

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Li-Fraumeni syndrome (LFS) is a rare high-penetrance and autosomal-dominant pathological condition caused by the germline mutation of the TP53 gene, predisposing to the development of tumors from pediatric age. We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/Pubmed and MeSH Database using the terms “Li-Fraumeni” AND “pediatric high-grade glioma (HGG)”, identifying six cases of HGGs in pediatric patients with LFS. We added a further case with peculiar features such as no familiar history of LFS, association of embryonal rhabdomyosarcoma and bithalamic HGG, whose immunohistochemical profile was accurately defined by Next Generation Sequencing. Knowledge synthesis and case analysis grounded the discussion about challenges in the management of this pathology in pediatric age.

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“…In GBM oncogenesis, the initial sequence of oncogenic changes may vary as GBM occurs in sporadic manner and as well as part of other syndromes including in NF1, with loss of P53 in Li-Fraumeni syndrome and others [ 155 , 207 – 209 ].…”

Section: Discussionmentioning

confidence: 99%

Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review

Shafi

Siddiqui

2022

World J Surg Onc

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Background Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons. Methods Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes. Results The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression. Conclusion Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.

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Gliomas arising in the setting of Li-Fraumeni syndrome stratify into two molecular subgroups with divergent clinicopathologic features

Cited by 22 publications

References 13 publications

Malignant gliomas with H3F3A G34R mutation or MYCN amplification in pediatric patients with Li Fraumeni syndrome

Malignant gliomas with H3F3A G34R mutation or MYCN amplification in pediatric patients with Li Fraumeni syndrome

A Unique Case of Bilateral Thalamic High-Grade Glioma in a Pediatric Patient with LI-Fraumeni Syndrome: Case Presentation and Review of the Literature

Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review

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