Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype

Justin S. Smith, Benjamin Alderete, Yuriko Minn, Thomas J. Borell, Arie Perry, Gayatry Mohapatra, Sandra M. Hosek, David Kimmel, Judith O'Fallon, Allan Yates, Burt G. Feuerstein, Peter C. Burger, Bernd W. Scheithauer, Robert B. Jenkins

Research output: Contribution to journalArticle

319 Scopus citations

Abstract

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas. Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Original languageEnglish (US)
Pages (from-to)4144-4152
Number of pages9
JournalOncogene
Volume18
Issue number28
DOIs
StatePublished - Jul 15 1999

Keywords

  • Chromosome 1
  • Chromosome 19
  • Comparative genomic hybridization
  • Diffuse glioma
  • Fluorescence in situ hybridization
  • Loss of heterozygosity
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Smith, J. S., Alderete, B., Minn, Y., Borell, T. J., Perry, A., Mohapatra, G., Hosek, S. M., Kimmel, D., O'Fallon, J., Yates, A., Feuerstein, B. G., Burger, P. C., Scheithauer, B. W., & Jenkins, R. B. (1999). Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene, 18(28), 4144-4152. https://doi.org/10.1038/sj.onc.1202759