Characterization of iPSCs derived from low grade gliomas revealed early regional chromosomal amplifications during gliomagenesis

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling.

Download Full-text

Cellular and molecular characterization of IDH1-mutated diffuse low grade gliomas reveals tumor heterogeneity and absence of EGFR/PDGFRα activation

Glia ◽

10.1002/glia.23240 ◽

2017 ◽

Vol 66 (2) ◽

pp. 239-255 ◽

Cited By ~ 6

Author(s):

S. Azar ◽

N. Leventoux ◽

C. Ripoll ◽

V. Rigau ◽

C. Gozé ◽

...

Keyword(s):

Molecular Characterization ◽

Tumor Heterogeneity ◽

Low Grade ◽

Low Grade Gliomas

Download Full-text

Patient-specific characterization of the invasiveness and proliferation of low-grade gliomas using serial MR imaging and a mathematical model of tumor growth

Oncology Reports ◽

10.3892/or.2015.3926 ◽

2015 ◽

Vol 33 (6) ◽

pp. 2883-2888 ◽

Cited By ~ 4

Author(s):

LEITH HATHOUT ◽

BENJAMIN M. ELLINGSON ◽

TIMOTHY F. CLOUGHESY ◽

WHITNEY B. POPE

Keyword(s):

Mathematical Model ◽

Mr Imaging ◽

Tumor Growth ◽

Patient Specific ◽

Low Grade ◽

Low Grade Gliomas

Download Full-text

Histogram Analysis of Diffusion Weighted Imaging in Low-Grade Gliomas: in vivo Characterization of Tumor Architecture and Corresponding Neuropathology

Frontiers in Oncology ◽

10.3389/fonc.2020.00206 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 2

Author(s):

Georg Alexander Gihr ◽

Diana Horvath-Rizea ◽

Elena Hekeler ◽

Oliver Ganslandt ◽

Hans Henkes ◽

...

Keyword(s):

Diffusion Weighted Imaging ◽

Histogram Analysis ◽

Low Grade ◽

Low Grade Gliomas ◽

Diffusion Weighted ◽

In Vivo Characterization

Download Full-text

Pediatric low-grade gliomas: molecular characterization of patient-derived cellular models

Child s Nervous System ◽

10.1007/s00381-020-04559-w ◽

2020 ◽

Author(s):

Martina Chiacchiarini ◽

Zein Mersini Besharat ◽

Andrea Carai ◽

Evelina Miele ◽

Giada Del Baldo ◽

...

Keyword(s):

Molecular Characterization ◽

Low Grade ◽

Low Grade Gliomas ◽

Cellular Models

Download Full-text

A Profound Basic Characterization of eIFs in Gliomas: Identifying eIF3I and 4H as Potential Novel Target Candidates in Glioma Therapy

Cancers ◽

10.3390/cancers13061482 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1482

Author(s):

Stefanie Krassnig ◽

Christina Wohlrab ◽

Nicole Golob-Schwarzl ◽

Andrea Raicht ◽

Christoph Schatz ◽

...

Keyword(s):

Gene Expression ◽

Low Grade ◽

Low Grade Gliomas ◽

Initiation Factors ◽

Upstream Regulator ◽

Current Therapies ◽

Novel Target ◽

Cell Growth And Proliferation ◽

Future Therapy

Glioblastoma (GBM) is an utterly devastating cerebral neoplasm and current therapies only marginally improve patients’ overall survival (OS). The PI3K/AKT/mTOR pathway participates in gliomagenesis through regulation of cell growth and proliferation. Since it is an upstream regulator of the rate-limiting translation initiation step of protein synthesis, controlled by eukaryotic initiation factors (eIFs), we aimed for a profound basic characterization of 17 eIFs to identify potential novel therapeutic targets for gliomas. Therefore, we retrospectively analyzed expressions of mTOR-related proteins and eIFs in human astrocytoma samples (WHO grades I–IV) and compared them to non-neoplastic cortical control brain tissue (CCBT) using immunoblot analyses and immunohistochemistry. We examined mRNA expression using qRT-PCR and additionally performed in silico analyses to observe the influence of eIFs on patients’ survival. Protein and mRNA expressions of eIF3B, eIF3I, eIF4A1, eIF4H, eIF5 and eIF6 were significantly increased in high grade gliomas compared to CCBT and partially in low grade gliomas. However, short OS was only associated with high eIF3I gene expression in low grade gliomas, but not in GBM. In GBM, high eIF4H gene expression significantly correlated with shorter patient survival. In conclusion, we identified eIF3I and eIF4H as the most promising targets for future therapy for glioma patients.

Download Full-text