MOLECULAR-GENETIC ALTERATIONS IN PLEOMORPHIC XANTHOASTROCYTOMA

Pleomorphic xanthoastrocytoma (PXA) is a low-grade glioma that may rec ur as a malignant diffuse astrocytoma such as glioblastoma (GEM). Whil e the molecular genetic basis of diffuse astrocytomas has been studied extensively, PXAs have not been analyzed in detail. We, therefore ana lyzed DNA from archival primary and recurrent PXAs from eight patients (three grade II PXAs without recurrence, one grade II PXA with recurr ence as grade Il PXA, two grade II PXAs with progression to GEM, and t wo grade III anaplastic PXAs with recurrence as grade III anaplastic P XA or GEM) for genetic changes associated with diffuse astrocytomas. S ingle-strand conformation polymorphism analysis of p53 exons 5-8 revea led migration shifts in two cases, one primary PXA without recurrence and one recurrent grade II PXA in which the primary tumor did not show a shift. DNA sequencing showed two missense mutations in codons 220 ( exon 6) and 292 (exon 8), respectively, mutations which have not been previously noted in astrocytomas. Differential polymerase chain reacti on analysis demonstrated epidermal growth factor receptor gene amplifi cation in only one tumor, a GEM without allelic loss of chromosome 10 that was the second GEM recurrence of an initial grade II PXA. Loss of heterozygosity studies on tumors from five patients, using three micr osatellite polymorphisms on chromosome 10q and three on chromosome 19q , did not disclose allelic loss in any recurrent tumor. These findings suggest that the genetic events that underlie PXA formation and progr ession may differ significantly from those involved in diffuse astrocy toma tumorigenesis.