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

Abstract

Summar y 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.

Long-term survival and transmission of INI1-mutation via nonpenetrant males in a family with rhabdoid tumour predisposition syndrome

“…Extraction of constitutional DNA from blood leukocytes was performed as described previously (Hulsebos et al, 1999).…”

“…To determine the mechanism by which these losses occurred, we extended previously reported haplotype and LOH analyses (Hulsebos et al, 1999). The key genetic events are summarised in Figure 1.…”

“…Here, we present an extended molecular analysis of a previously reported family in which four cousins were affected with an MBT at young age (Hulsebos et al, 1999). These tumours were originally classified as anaplastic ependymomas (Nijssen et al, 1994).…”

“…These tumours were originally classified as anaplastic ependymomas (Nijssen et al, 1994). However, because of the previously documented involvement of chromosome 22 in the inheritance of the predisposition to these tumours (Hulsebos et al, 1999) and the possibility of misclassification, we investigated whether these anaplastic ependymomas were in fact AT/RTs. This proved to be the case, as we concluded from re-evaluation of their histopathology and from mutation and expression analysis of the INI1 gene in three of these tumours.…”

Clear cell ependymoma: A clinicopathologic and radiographic analysis of 10 patients

“…Clearly distinct from astrocytomas and oligodendrogliomas at the molecular level, the most frequently reported abnormality is deletion of chromosome 22. [5][6][7][8][9][10][11][12][13][14][15] Gains of chromosome 1q (16 -18) and losses involving chromosomes 22q (16), 6q (19), and 17p (11) appear to be particularly prevalent in pediatric examples. In a recent study by Singh et al, NF2 and DAL-1, two members of the protein 4.1 superfamily, were implicated in the pathogenesis of ependymomas.…”