title: Genetic alterations commonly found in diffusely infiltrating cerebral gliomas are rare or absent in pleomorphic xanthoastrocytomas.
abstract: Pleomorphic xanthoastrocytoma (PXA) is a rare, usually well-circumscribed and superficially located neoplasm that preferentially arises in the cerebral cortex of children and young adults. The molecular aberrations that are associated with these tumors have not been studied systematically so far. We here report on a molecular genetic analysis of 62 PXAs (46 PXAs of World Health Organization [WHO] grade II and 16 PXAs with anaplastic features) for alterations of 5 candidate genes known to be frequently aberrant in diffusely infiltrating astrocytic gliomas, i.e. TP53, CDKN2A (p16(INK4a)), CDK4, MDM2, and EGFR. Only 3 PXAs (5%) carried a TP53 mutation. None of the 62 PXAs had lost both copies of the CDKN2A gene. The CDK4, MDM2, or EGFR genes were not amplified in any of the tumors. Fourteen PXAs were additionally analyzed for loss of heterozygosity (LOH) at microsatellite markers located on the chromosomes/chromosomal arms 1, gp, 9p, 10, 17, 19q, and 22q. Two PXAs (14%) had LOH at all informative markers on 9p, while 1 PXA demonstrated an interstitial area of allelic imbalance between D22S533 and D22S417 at 22q11.2-q13.3. Further analysis of 10 PXAs for inactivation of the CDKN2A. p14(ARF), and CDKN2B (p15(INK4b)) genes on 9p21 did not reveal any homozygous deletion, mutation, promoter hypermethylation, or complete loss of mRNA expression. Taken together, our results indicate that the chromosomal and genetic aberrations in PXAs are different from those typically associated with the diffusely infiltrating astrocytic and oligodendroglial gliomas. These genetic differences likely contribute to the more favorable behavior of PXAs and may be helpful for the molecular differential diagnosis of cerebral gliomas.
authors.affiliation: Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kaulich
authors.forename: Britta
authors.initials: B
authors.lastname: Blaschke
authors.forename: Astrid
authors.initials: A
authors.lastname: Nümann
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Ruthild G
authors.initials: RG
authors.lastname: Weber
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D066246:ErbB Receptors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases