Introduction: The methylation of tumor suppressor genes has been implicated as an important mechanism triggering the tumorigenesis. BRCA1 (17q21) are classically associated with susceptibility to hormone-dependent cancers, especially breast and ovarian tumors. The higher incidence of meningiomas in females and the proliferation in response to hormones prompted the possible impact of BRCA1 methylation in menigothelial tumors and stirring interest for your research also in glial tumors.
Methods: We analyze the methylation status of BRCA1 by MSP-PCR in 42 gliomas (30 astrocytomas and 12 oligodendrogliomas) and 33 meningiomas of different histopathological grades.
Results: The distribution by age, sex, tumor location and histopathology of patients reproduced, in general, global trends. BRCA1 methylation was observed in 60% of tumors (70% of astrocytomas, 33% of oligodendrogliomas and 58% of meningiomas). For meningiomas, an association between BRCA1 methylation and male gender was evident (p = 0.0009). Astrocytomas showed a higher rate of methylation compared to oligodendrogliomas (p =0.01). The occurrence of methylation tended to decrease in high grade tumors.
Conclusions: It is suggested that the BRCA1 methylation in gliomas may be associated to the TP53 gene alterations and its reduction among the most malignant tumors reflects the smaller contribution of this suppressor compared to other genetic alterations, such as EGFR amplification. In meningiomas, BRCA1 methylation seems to leave the meningothelial cells mercy to the mitogenic effects of estrogen, especially in low hormonal rate condition. Additionally, the absence of BRCA1 for DNA repair could contribute to the accumulation of more genetic disorders that lead to the oncogenesis
Patient Care: These results may contribute to the identification of a new subset of meningioma, as well as indicate a new therapeutic approach for gliomas and meningiomas.
Learning Objectives: New molecular markers for gliomas and meningiomas.