H3 G34-mutant high-grade glioma
Ka Young Lim1, Jae Kyung Won1,2, Chul-Kee Park3,2
1Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Brain Tumor Pathology
|September 30, 2020
Summary
H3.3 G34-mutant high-grade gliomas are rare brain tumors with distinct genetic profiles. These gliomas show a better median survival than IDH-wildtype glioblastomas but worse than IDH-mutant glioblastomas.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Genetics
Background:
- H3F3A G34 (H3.3 G34)-mutant high-grade gliomas (HGG) are rare, newly recognized infiltrating gliomas of the cerebral hemisphere.
- Understanding their clinicopathological and molecular characteristics is crucial for comparison with other glioma subtypes.
Purpose of the Study:
- To report the clinicopathological and molecular characteristics of four H3.3 G34-mutant gliomas.
- To compare their biological behavior with glioblastomas (GBMs) and H3 K27M-mutant diffuse midline gliomas (DMGs).
Main Methods:
- Clinicopathological analysis of four H3.3 G34-mutant glioma cases.
- Molecular profiling including genetic and epigenetic signatures (ATRX, MGMT promoter, Olig2, IDH, TERT promoter).
Main Results:
- The median age of patients was 44.5 years, with tumors primarily in the cerebral hemisphere.
- Tumors were high-grade but lacked microvascular proliferation and necrosis.
- Uniform genetic/epigenetic signatures: ATRX-mutant, MGMT promoter-methylated, Olig2-negative, IDH- and TERT promoter-wildtype.
- Median survival was 23.5 months, better than IDH-wildtype GBMs and H3 K27M-mutant DMGs, but worse than IDH-mutant GBMs.
Conclusions:
- H3.3 G34-mutant gliomas are unique HGGs with consistent genetic/epigenetic abnormalities, suggesting a single origin.
- Prognosis is influenced by tumor infiltration and resectability.
