Evidence for an ependymoma tumour suppressor gene in chromosome region 22pter–22q11.2

Ependymomas are glial tumours of the brain and spinal cord. The most frequent genetic change in sporadic ependymoma is monosomy 22, suggesting the presence of an ependymoma tumour suppressor gene on that chromosome. Clustering of ependymomas has been reported to occur in some families. From an earlier study in a family in which four cousins developed an ependymoma, we concluded that an ependymoma-susceptibility gene, which is not the NF2 gene in 22q12, might be located on chromosome 22. To localize that gene, we performed a segregation analysis with chromosome 22 markers in this family. This analysis revealed that the susceptibility gene may be located proximal to marker D22S941 in 22pter–22q11.2. Comparative genomic hybridization showed that monosomy 22 was the sole detectable genetic aberration in the tumour of one of the patients. Loss of heterozygosity studies in that tumour revealed that, in accordance to Knudson’s two-hit theory of tumorigenesis, the lost chromosome 22 originated from the parent presumed to have contributed the wild-type allele of the susceptibility gene. Thus, our segregation and tumour studies collectively indicate that an ependymoma tumour suppressor gene may be present in region 22pter–22q11.2. © 1999 Cancer Research Campaig

Unilateral pallidotomy in Parkinson's disease: a randomised, single-blind, multicentre trial

Background The results of several cohort studies suggest that patients with advanced Parkinson's disease would benefit from unilateral pallidotomy. We have assessed the efficacy of unilateral pallidotomy in a randomised, single-blind, multicentre trial. Methods We enrolled 37 patients with advanced Parkinson's disease who had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia, Patients were randomly assigned to unilateral pallidotomy within 1 month or to pallidotomy after the primary outcome assessment (6 months later). The primary outcome was the difference between the groups in median changes on the motor examination section of the unified Parkinson's disease rating scale (UPDRS 3) score done in the off phase. Secondary outcome measures included levodopa-induced dyskinesias (dyskinesia rating scale [DRS]) and extent of disability (UPDRS 2). Findings The median UPDRS 3 off score of the pallidotomy patients improved from 47 to 32.5, whereas that of control patients slightly worsened from 52.5 to 56.5 (p <0.001). In the on phase the median DRS score improved 50% in pallidotomy patients compared with no change in controls. The UPDRS 2 off score improved with a median of 7 in the pallidotomy group. Two treated patients had major adverse effects. Interpretation Unilateral pallidotomy is an effective treatment in patients with advanced Parkinson's disease, who have an unsatisfactory response to pharmacological treatment