Diffusely infiltrating astrocytomas: pathology, molecular mechanisms and markers
Koichi Ichimura1, Yoshitaka Narita, Cynthia E Hawkins
1Division of Brain Tumor Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan, kichimur@ncc.go.jp.
Acta Neuropathologica
|May 16, 2015
Summary
Molecular genetics reveals two main types of diffuse astrocytomas. Understanding these genetic differences, particularly IDH mutations, is crucial for predicting prognosis and guiding personalized treatment strategies for brain tumors.
Area of Science:
- Neuro-oncology
- Molecular genetics
- Cancer classification
Background:
- Diffusely infiltrating astrocytomas (WHO grade II and III) are classified under astrocytic tumors.
- Prognosis is determined by the timing of malignant progression, despite generally longer survival than glioblastoma.
- Histopathological diagnosis may mask distinct genetic tumor groups.
Purpose of the Study:
- To explore the molecular genetic landscape of diffusely infiltrating astrocytomas.
- To identify genetic markers for distinct pathogenic and prognostic groups.
- To inform individualized therapeutic strategies based on molecular profiles.
Main Methods:
- Analysis of genetic mutations in diffusely infiltrating astrocytomas.
- Comparison of genetic profiles between different WHO grades and age groups.
- Correlation of molecular subtypes with clinical outcomes.
Main Results:
- Most diffuse astrocytomas (WHO II/III) share mutations in IDH1/IDH2, TP53, and ATRX.
- No genetic markers distinguish between WHO grade II and III in IDH-mutated astrocytomas.
- IDH-wildtype astrocytomas exhibit distinct genotypes and glioblastoma-like prognoses.
- Pediatric diffuse astrocytomas lack IDH/TP53 mutations, showing BRAF or MYB/MYBL1/FGFR1 alterations.
Conclusions:
- Molecular classification can delineate distinct pathogenic and prognostic groups of diffuse astrocytomas.
- Genetic profiling, especially IDH status, is key to understanding tumor behavior.
- Molecular insights are essential for developing tailored treatment approaches for astrocytomas.
