Detection of p16, RB, CDK4, and p53 gene deletion and amplification by fluorescence in situ hybridization in 96 gliomas

Arie Perry, Kari Anderl, Tom J. Borell, David W. Kimmel, Chiao H. Wang, Judith R. O'Fallon, Burt G. Feuerstein, Bernd W. Scheithauer, Robert B. Jenkins

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Inactivation of the p53 gene is a common early event of astrocytoma tumorigenesis. Alternatively, since the p16, retinoblastoma (RB), and CDK4 genes have been implicated in malignant progression, detection of losses or amplifications of these genes in gliomas could be diagnostically, prognostically, and therapeutically important. We obtained smear preparations from 96 diffuse gliomas and 10 nonneoplastic specimens. Dual-color fluorescence in situ hybridizations using paired probes for CEN9/p16, CEN8/RB, CEN17/p53, and CEN12/CDK4 were performed and revealed expected frequencies of abnormalities, except for p53 losses, which were low (7%). The latter supports the concept that p53 inactivation usually occurs by mitotic recombination. Detected abnormalities of the p16/RB/CDK4 pathway were highly associated with astrocytic differentiation and were univariately associated with decreased patient survival. However, only patient age and histologic classification retained statistical significance on multivariate analysis. We conclude that in diffuse gliomas, p16/RB/CDK4 abnormalities are markers of astrocytic phenotype. Thus, their detection by fluorescence in situ hybridization may have diagnostic usefulness in cases with equivocal morphologic features. Although our numbers are small, we find no additional prognostic significance to these genetic abnormalities once age, grade, and oligodendroglial histology are taken into account.

Original languageEnglish (US)
Pages (from-to)801-809
Number of pages9
JournalAmerican journal of clinical pathology
Volume112
Issue number6
DOIs
StatePublished - 1999

Keywords

  • Astrocytoma
  • Cyclin-dependent kinases
  • Fluorescence in situ hybridization
  • Glioma
  • Retinoblastoma gene
  • p16 gene
  • p53 gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Perry, A., Anderl, K., Borell, T. J., Kimmel, D. W., Wang, C. H., O'Fallon, J. R., Feuerstein, B. G., Scheithauer, B. W., & Jenkins, R. B. (1999). Detection of p16, RB, CDK4, and p53 gene deletion and amplification by fluorescence in situ hybridization in 96 gliomas. American journal of clinical pathology, 112(6), 801-809. https://doi.org/10.1093/ajcp/112.6.801