Amplification of the gli Gene in Childhood Sarcomas

W. Mark Roberts, Edwin C. Douglass, Stephen C. Peiper, Peter J Houghton, A. Thomas Look

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

The gli gene, originally identified by its amplified copy number in cells from a human malignant glioma, has a predicted translation product that contains five tandem DNA-binding zinc finger motifs related to those of Krüppel, a developmentally important Drosophila segmentation gene. Because of the potential importance of overproduction of this protein in neoplastic development, we examined DNAs from 29 cases of childhood sarcoma for evidence of amplification of the gli gene. In one of the 13 rhabdomyosarcomas studied, genomic DNA restriction fragments containing the gli gene were amplified approximately 30-fold, and expression of the 4.0-kilobase gli mRNA transcript was identified. The tumor with gli gene amplification lacked the usual histological features of alveolar or embryonal rhabdomyosarcoma; however, ultrastructural analysis of tumor cells established in culture revealed attenuated sarcomeres, resembling those found in primitive rhabdomyoblasts. Cytogenetic analysis of this cell line disclosed double-minute chromatin bodies, with no apparent rearrangements in the region of the gli locus on the long arm of chromosome 12, bands q13 to q14.3. A 15-fold level of gli amplification and gli mRNA transcripts were also detected in an established cell line from a patient with a rare form of osteosarcoma characterized by multipotential histological features. A similar level of gli gene amplification was observed in cryopreserved primary tumor cells from this patient, confirming that gene amplification took place during tumor development and not during in vitro cell culture. Amplified gli sequences were cytogenetically localized by in situ hybridization to a homogeneously staining region contained on a derivative chromosome 7. Of eight osteosarcomas and seven Ewing's sarcomas with typical histopathological features, none had detectable rearrangements or amplification of gli sequences. Thus, gli gene amplification in childhood sarcomas appears restricted to tumors with primitive histopathological features, perhaps reflecting overproduction of a gene product able to influence gene expression during early mesenchymal cell development.

Original languageEnglish (US)
Pages (from-to)5407-5413
Number of pages7
JournalCancer Research
Volume49
Issue number19
StatePublished - Oct 1 1989
Externally publishedYes

Fingerprint

Gene Amplification
Sarcoma
Osteosarcoma
Neoplasms
Genes
DNA
Alveolar Rhabdomyosarcoma
Embryonal Rhabdomyosarcoma
Cell Line
Chromosomes, Human, Pair 12
Messenger RNA
Sarcomeres
Ewing's Sarcoma
Chromosomes, Human, Pair 7
Rhabdomyosarcoma
Cytogenetic Analysis
Zinc Fingers
Glioma
Drosophila
Chromatin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Roberts, W. M., Douglass, E. C., Peiper, S. C., Houghton, P. J., & Look, A. T. (1989). Amplification of the gli Gene in Childhood Sarcomas. Cancer Research, 49(19), 5407-5413.

Amplification of the gli Gene in Childhood Sarcomas. / Roberts, W. Mark; Douglass, Edwin C.; Peiper, Stephen C.; Houghton, Peter J; Look, A. Thomas.

In: Cancer Research, Vol. 49, No. 19, 01.10.1989, p. 5407-5413.

Research output: Contribution to journalArticle

Roberts, WM, Douglass, EC, Peiper, SC, Houghton, PJ & Look, AT 1989, 'Amplification of the gli Gene in Childhood Sarcomas', Cancer Research, vol. 49, no. 19, pp. 5407-5413.
Roberts WM, Douglass EC, Peiper SC, Houghton PJ, Look AT. Amplification of the gli Gene in Childhood Sarcomas. Cancer Research. 1989 Oct 1;49(19):5407-5413.
Roberts, W. Mark ; Douglass, Edwin C. ; Peiper, Stephen C. ; Houghton, Peter J ; Look, A. Thomas. / Amplification of the gli Gene in Childhood Sarcomas. In: Cancer Research. 1989 ; Vol. 49, No. 19. pp. 5407-5413.
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