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MicroRNAs (miRNAs) are short non-protein-coding RNAs that function as key regulators of diverse biological processes through negative control on gene expression at the post-transcriptional level. Emerging evidence indicates that miRNAs play an important role in the development of human cancers, with their deregulation resulting in altered activity of downstream tumor suppressors, oncogenes and other signaling molecules. Recent years have seen considerable progress in miRNA research in brain tumors, particularly in glioblastomas and medulloblastomas, providing novel insights into the pathogenesis of these malignant lesions. Expression profiling has unveiled miRNA signatures that not only distinguish brain tumors from normal tissues, but can also differentiate histotypes or molecular subtypes with altered genetic pathways. Moreover, specific miRNA subsets may have potential diagnostic and prognostic values in some brain tumors. Several deregulated miRNAs uncovered in glioblastomas and medulloblastomas have their gene targets and the associated genetic pathways identified. This review summarizes recent findings of miRNA study in brain tumors.

The INK4a/ARF locus on chromosome 9p21 encodes two gene products that are involved in cell cycle regulation through inhibition of CDK4-mediated RB phosphorylation (p16INK4a) and binding to MDM2 leading to p53 stabilization (p14ARF). The locus is deleted in up to 25% of oligodendrogliomas and 50% of anaplastic oligodendrogliomas, but little is known on the frequency of gene silencing by DNA methylation. We assessed promoter hypermethylation of p14ARF and p16INK4a using methylation-specific PCR, and homozygous deletion of the p14ARF and p16INK4a genes by differential PCR in 29 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III). Promoter hypermethylation of the p14ARF gene was detected in 6/29 (21%) oligodendrogliomas and 3/20 (15%) anaplastic oligodendrogliomas. None of the oligodendrogliomas and only 1 out of 20 anaplastic oligodendrogliomas showed hypermethylation of p16INK4a. Homozygous deletion was not detected in any of the WHO grade II oligodendrogliomas but was present in 5/20 (25%) anaplastic oligodendrogliomas and always affected both genes. In one tumor containing distinct areas with and without anaplasia, p14ARF hypermethylation was detected in the WHO grade II area, while homozygous co-deletion of p14ARF and p16INK4a was found in the region with anaplastic features (grade III). These data suggest that aberrant p14ARF expression due to hypermethylation is the earliest INK4a/ARF change in the evolution of oligodendrogliomas, while the presence of p14ARF and p16INK4a deletions indicates progression to anaplastic oligodendroglioma.

We report a typical case of so called "volvular epilepsy" (synonym: retatory seizures, circling epilepsy). Our 59-year-old patient exhibited the characteristic pattern of repetitive walking in small circles, always strictly contralateral to the epileptogenic focus in the right fronto-parietal region. The MRI study indicated a diagnosis of brain tumor in the same area, which was confirmed as an oligodendroglioma. After adequate anticonvulsive treatment there was complete seizure control. Rotatory seizures are rarely reported and usually related to pathological findings in the fronto-temporal region (infarction, neoplasma, giant aneurysm and posttraumatic lesions). Corresponding to the international classification of epileptic seizures, this is a very rare manifestation of a simple partial seizure (without impairment of the conscious state), which can extend to a complex partial seizure (with impairment of consciousness) and secondarily generalized tonic-clonic seizure. In explaining this rare epileptic phenomenon, the controversial concepts (involvement of the striatum, temporal lobe or cortical adverse fields?) are discussed.