A family with spinal anaplastic ependymoma: evidence of loss of chromosome 22q in tumor

Abstract

Familial ependymal tumors are a very rare disease, the pathogenesis of which is unknown. Previous studies indicate an involvement of tumor suppressor genes localized within chromosomal region 22q, whereas details are still unclear. Here we report a non-neurofibromatosis type-2 (non-NF2) Japanese family in which two of the four members are affected with cervical spinal cord ependymoma, and one of the four is affected with schwannoma. Loss of heterozygosity (LOH) studies were carried out searching for common allelic loss at chromosomal region 22q11.2-qtel in two of the affected patients. Our findings support a prediction for existence of a tumor suppressor gene on chromosome 22 especially related to the tumorigenesis of familial ependymal tumors.

Familial intracranial ependymomas

“…Furthermore, the literature includes several descriptions of families with more than one member with CNS tumors, at least one of which was an ependymoma in the absence of neurofibromatosis (a condition that predisposes the patient to the development of ependymomas 33 ) or other hereditary CNS tumor syndromes (Table 1). We reviewed nine previously published studies of families in which ependymomas were diagnosed in at least one family member.…”

“…Genotype analysis in one of these tumors showed a subpopulation of tumor cells with monosomy of chromosome 22, supporting the role of a tumor suppressor gene on chromosome 22 in the pathogenesis of familial ependymal tumors. Similarly, Yokota, et al, 33 have described a four-member Japanese family in which two members had cervical and thoracic spinal cord ependymomas and another had a cervical nerve root schwannoma. Molecular genetic analysis of the spinal anaplastic ependymomas supported the existence of a tumor suppressor gene on chromosome 22 that appears to be involved in the pathogenesis of familial ependymal tumors.…”

“…10,21,24 Approximately 30% of ependymomas demonstrate monosomy of chromosome 22. 33 Kraus, et al, 16 who analyzed 53 cases of sporadic ependymal tumors (18 in children and 35 in adults), have found a high frequency of allelic loss on chromosome arm 22q. They have concluded that this region may harbor putative tumor suppressor gene or genes that are involved in the evolution and/or progression of human ependymal tumors.…”

“…4,15,26,31,32 Furthermore, the familial occurrence of ependymomas has been described in the literature. 5,12,20,25,27,33 We report the cases of two members of a family in which three family members had ependymomas. The father and his son were treated for fourth ventricular ependymomas at our institution, and the father's sister was treated at another institution for an ependymoma of the posterior fossa.…”

Merlin Expression in Pediatric Anaplastic Ependymomas Real Time PCR Study

“…Among ependymomas, NF2 mutations are primarily encountered in spinal lesions. In contrast, it has been assumed that NF2 alterations do not significantly vary with tumor grade [1,2,9,13,18,20,21,25].…”