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

Ependimomas: achados clínicos, epidemiológicos e anatomopatológicos de 22 casos Ependymonas: clinical, epidemiological and pathological findings of 22 cases

Ependimomas são neoplasias compostas por células ependimárias neoplásicas, manifestando-se predominantemente em crianças e adultos jovens. Relatamos os achados clínicos, epidemiológicos e anatomopatológicos de 22 casos de ependimomas. Dos 22 casos analisados, 14 ocorreram em pacientes do sexo masculino e 8 em pacientes femininos. As idades variaram de 1 a 58 anos, com média de 24,63 anos. Quanto à localização, 10 casos acometeram medula, 7 ocorreram em hemisférios cerebrais, 2 intraventriculares e 1 no tronco cerebral. Os sinais e sintomas observados incluiram redução da força muscular (59,1% dos pacientes), alterações da marcha (36,3%), alterações da sensibilidade(36,3%), hiperreflexia e sindrome de hipertensão endocraniana, com período de evolução variando de 15 dias a 8 anos, com média de 17,58 meses. Sete pacientes foram submetidos a ressecção cirúrgica total , 7 a exérese parcial, 4 a exérese parcial associada a radioterapia adjuvante, 3 a ressecção parcial seguida de quimioterapia e 1 a tumorectomia total associada a radioterapia. Evidenciou-se taxa de recidiva tumoral total de 18,2%. Estes achados aproximam-se dos encontrados na literatura internacional, corroborando para a compreensão do comportamento biológico deste tumor.<br>Ependymomas are composed of neoplastic ependymal cells, affecting mainly children and young adults. We report the clinical and pathological findings of 22 cases of ependymomas. Fourteen patients were males and 8 were females. The ages ranged between 1 and 58 years, with a mean of 24.63 years. The symptoms reflected the growth and topography of the tumours; muscle weakness (59.1%), gait disorders (36.3%), sensitive disorders (36.3%), hyperreflexia and intracranial hypertension syndrome were the most frequent symptoms. Ten tumours affected the medulla, 7 the cerebral hemispheres, 2 the cerebral ventricles and 1 brain stem. Seven patients were submitted total resection of the tumor, from which one received adjuvant radiotherapy. 15 other patients were submitted to partial resection; from which 4 received adjuvant radiotherapy, 3 adjuvant chemotherapy and 1 chemotherapy and radiotherapy. The recurrence rate was 18.2%. These results are similar with the literature and may contribute to further understanding the biological behavior of these tumours

Genetic abnormalities detected in ependymomas by comparative genomic hybridisation

Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P&lt;0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P&lt;0.0005) in tumours from adults and the spinal region. Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities - gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14 - varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively. Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies