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 freque nt genetic change in sporadic ependymoma is monosomy 22, suggesting the pre sence of an ependymoma tumour suppressor gene on that chromosome. Clusterin g of ependymomas has been reported to occur in some families, From an earli er study in a family in which four cousins developed an ependymoma, we conc luded that an ependymoma-susceptibility gene, which is not the NF2 gene in 22q12, might be located on chromosome 22, To localize that gene, we perform ed a segregation analysis with chromosome 22 markers in this family. This a nalysis revealed that the susceptibility gene may be located proximal to ma rker D22S941 in 22pter-22q11.2. Comparative genomic hybridization showed th at 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 tumo ur studies collectively indicate that an ependymoma tumour suppressor gene may be present in region 22pter-22q11.2. (C) 1999 Cancer Research Campaign.