title: Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas.
abstract: OBJECTIVE
  While it is well known that pilocytic astrocytomas are clinically distinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic astrocytomas for genetic alterations that are commonly seen in diffuse astrocytomas.
  
  
  RESULTS
  By using molecular genetic and immunohistochemical techniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocytomas. Mutation screening of p53 and PTEN was performed by single strand conformation polymorphism analysis followed by direct sequencing. Loss of heterozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsatellite markers and genomic microsatellite instability (MSI) was also screened. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohistochemistry. Five tumours were found to have single genetic alterations, which included a p53 mutation, a PTEN mutation, MSI at a single microsatellite marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. Protein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively. Significantly and in sharp contrast to diffuse astrocytomas, no pilocytic astrocytoma in our series stained for p53 protein.
  
  
  CONCLUSIONS
  Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p116 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small neurosurgical biopsies.
authors: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong.
authors: Y
authors: Y
authors: Cheng
authors: J C
authors: JC
authors: Pang
authors: H K
authors: HK
authors: Ng
authors: M
authors: M
authors: Ding
authors: S F
authors: SF
authors: Zhang
authors: J
authors: J
authors: Zheng
authors: D G
authors: DG
authors: Liu
authors: W S
authors: WS
authors: Poon
mesh_terms: D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human