Molecular genetic analysis of chromosome arm 17p and chromosome arm 22q DNA sequences in sporadic pediatric ependymomas

Abstract

Ependymomas are glial tumors of the brain and spinal cord occurring both sporadically and in a familial syndrome, neurofibromatosis type 2 (NF2). Previous analyses performed on specimens obtained predominantly from adult patients have shown loss of DNA sequences from chromosome arm 22q, which is the location of the NF2 gene. Previously, we documented the consistent loss of chromosome arm 17p DNA in medulloblastoma and astrocytoma, which are the most common brain tumors in children. Although mutation of the TP53 gene located on 17p is the most frequent genetic mutation in all adult tumor types, such mutations are rare in most childhood brain tumors investigated to date. We studied a series of pediatric ependymoma specimens (16 intracranial and 2 spinal) for loss of 17p and 22q DNA sequences and for mutation of the TP53 and NF2 genes. None of the children had the clinical stigmata of NF2. We detected loss of 17p DNA sequences in 9 of the 18 specimens (50%); in 7 of 9 of these specimens (78%), the 144-D6 marker was deleted. In contrast, only 2 of these same 18 specimens (11%) showed loss of 22q DNA. One TP53 gene mutation was detected in a child from a cancer kindred. No mutations were detected in the NF2 gene. Our results suggest that loss of chromosome arm 17p DNA sequences is common in sporadic pediatric ependymomas and that, in contrast to ependymomas in adults, deletion of chromosome arm 22q sequences is rare. Furthermore, TP53 and NF2 gene mutations do not play an important role in the etiology of sporadic pediatric ependymomas.