Alterations in the RB Pathway With Inactivation of RB1 Characterize Glioblastomas With a Primitive Neuronal Component
Rati Chkheidze1,2, Jack Raisanen2, Jeffrey Gagan2
1From the Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Journal of Neuropathology and Experimental Neurology
|December 1, 2021
Summary
Molecular alterations in glioblastoma with a primitive neuronal component (G/PN) were investigated. Inactivation of the retinoblastoma tumor suppressor gene (RB1) in the RB pathway appears to drive G/PN development.
Area of Science:
- Neuro-oncology
- Molecular genetics
- Cancer biology
Background:
- Glioblastoma (GBM) can exhibit a primitive neuronal component (G/PN).
- Molecular drivers of the G/PN histologic variant are not well-defined.
Purpose of the Study:
- To identify molecular alterations associated with glioblastoma with a primitive neuronal component.
- To investigate the role of the RB pathway in G/PN.
Main Methods:
- Next-generation sequencing of 1500 tumor-related genes in 9 G/PN patient tumors.
- Analysis of 27 G/PN cases from The Cancer Genome Atlas (TCGA).
- Immunohistochemistry for RB protein expression.
Main Results:
- RB pathway alterations were found in all patient tumors and 81% of TCGA G/PN cases.
- The retinoblastoma tumor suppressor gene (RB1) was frequently affected.
- RB1 mutations showed significantly higher allelic fractions in G/PN compared to conventional glioblastomas.
- Loss of RB expression was observed in 78% of G/PN patients.
Conclusions:
- Alterations in the RB pathway are prevalent in glioblastoma with a primitive neuronal component.
- RB1 inactivation may be a key mechanism driving the G/PN phenotype.
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