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Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas.
Takao Watanabe1, Mitsutoshi Nakamura, Johan M Kros
1Unit of Molecular Pathology, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
Acta Neuropathologica
|March 22, 2002
Summary
Oligodendrogliomas with classic features often show 1p/19q loss, correlating with chemotherapy response. TP53 mutations are more common in astrocytomas, which lack this 1p/19q alteration, indicating distinct tumor biology and prognosis.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Cancer Genetics
Background:
- Distinguishing oligodendrogliomas from low-grade astrocytomas is challenging due to overlapping histology.
- Loss of heterozygosity (LOH) on chromosomes 1p and 19q is a hallmark of oligodendrogliomas and predicts chemotherapy response.
- TP53 mutations are frequent in low-grade astrocytomas and are associated with resistance to alkylating agents.
Purpose of the Study:
- To investigate the correlation between histological features and genetic profiles (TP53 mutations, 1p/19q LOH) in oligodendrogliomas and low-grade diffuse astrocytomas.
- To determine the prevalence of specific genetic alterations in these tumor types.
- To assess the potential of histological features to predict genetic status.
Main Methods:
- Screening of 19 oligodendrogliomas and 23 low-grade diffuse astrocytomas (WHO grade II) for TP53 mutations and 1p/19q LOH.
- Histological analysis focusing on features like perinuclear halos and vascular patterns.
- Assessment of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation.
Main Results:
- Oligodendrogliomas frequently exhibited 1p/19q LOH (79%) and occasional TP53 mutations (21%).
- Classical histological features in oligodendrogliomas were strongly associated with 1p/19q LOH (93%).
- Low-grade astrocytomas showed more frequent TP53 mutations (43%) and rare 1p/19q LOH (13%).
- TP53 mutations and 1p/19q LOH were mutually exclusive in both tumor types.
- MGMT promoter methylation was present in approximately half of both tumor types, without correlation to 1p/19q LOH.
Conclusions:
- Histological features can help identify oligodendrogliomas likely to possess 1p/19q LOH, suggesting a better prognosis.
- The genetic profiles of oligodendrogliomas and low-grade astrocytomas are distinct, with 1p/19q LOH and TP53 mutations serving as key differentiating markers.
- MGMT promoter methylation does not appear to be a reliable prognostic marker in oligodendrogliomas.