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Recurrent astrocytoma in a child: A report of cytogenetics and TP53 gene mutation screening

Departments of Pathology (A.D., W.M.M.), Child Neurology (J.M.F.), and Medical Genetics (E.v.d.B., V.M.H.), University Hospital of Groningen, The Netherlands

² Address correspondence and reprint requests to W.M. Molenaar, Department of Pathology, University Hospital of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

Abstract

An 8-year-old girl presented with a cerebral tumor and 3 recurrences within 15 months. The primary tumor was a low-grade astrocytoma, but the recurrences showed progressively malignant phenotypes with increasing mitotic activity and MIB-1 labeling indices. Radiotherapy was given between the first and the second recurrences. Cytogenetic analysis of the first and the second recurrences showed abnormal karyotypes. There seemed to be 2 common breakpoints in these 2 recurrences. TP53 gene mutation screening, using comprehensive denaturing gradient gel electrophoresis, revealed among others a possibly causative mutation of exon 5 in 3 of 4 tumor samples. The meaning of TP53 mutations in low-grade astrocytomas is still unclear, but the highly abnormal karyotypes, which are unusual in these tumors, probably provide genetic evidence for the unexpected aggressive behavior of the tumor in this patient.