Molecular genetic alterations in pleomorphic xanthoastrocytoma |
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| Authors: | Werner Paulus David K Lisle Jörg C Tonn Helmut K Wolf Wolfgang Roggendorf Steven A Reeves David N Louis |
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| Institution: | (1) Molecular Neuro-Oncology Laboratory, Neurosurgical Service and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA, US;(2) Institute of Neuropathology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland Fax: 41-1-255-4402, CH;(3) Department of Neurosurgery, University of Würzburg, Würzburg, Germany, DE;(4) Institute of Neuropathology, University of Bonn, Bonn, Germany, DE;(5) Institute of Pathology (Neuropathology), University of Würzburg, Würzburg, Germany, DE |
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| Abstract: | Pleomorphic xanthoastrocytoma (PXA) is a low-grade glioma that may recur as a malignant diffuse astrocytoma such as glioblastoma
(GBM). While the molecular genetic basis of diffuse astrocytomas has been studied extensively, PXAs have not been analyzed
in detail. We, therefore analyzed DNA from archival primary and recurrent PXAs from eight patients (three grade II PXAs without
recurrence, one grade II PXA with recurrence as grade II PXA, two grade II PXAs with progression to GBM, and two grade III
anaplastic PXAs with recurrence as grade III anaplastic PXA or GBM) for genetic changes associated with diffuse astrocytomas.
Single-strand conformation polymorphism analysis of p53 exons 5–8 revealed 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 reaction analysis demonstrated epidermal growth factor receptor gene amplification
in only one tumor, a GBM without allelic loss of chromosome 10 that was the second GBM recurrence of an initial grade II PXA.
Loss of heterozygosity studies on tumors from five patients, using three microsatellite 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 progression may differ significantly from those involved in diffuse astrocytoma tumorigenesis.
Received: 18 July 1995 / Revised, accepted: 15 September 1995 |
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| Keywords: | Astrocytoma Epidermal growth factor receptor Glioma p53 Loss of heterozygosity |
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