PMID- 2766305
OWN - NLM
STAT- MEDLINE
DCOM- 19891005
LR  - 20111117
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 49
IP  - 19
DP  - 1989 Oct 1
TI  - Amplification of the gli gene in childhood sarcomas.
PG  - 5407-13
AB  - 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 Kruppel, 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.
FAU - Roberts, W M
AU  - Roberts WM
AD  - Department of Hematology-Oncology, St. Jude Children's Research Hospital, 
      Memphis, TN 38101.
FAU - Douglass, E C
AU  - Douglass EC
FAU - Peiper, S C
AU  - Peiper SC
FAU - Houghton, P J
AU  - Houghton PJ
FAU - Look, A T
AU  - Look AT
LA  - eng
GR  - CA-21765/CA/NCI NIH HHS/United States
GR  - CA-23099/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Bone Neoplasms/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 12/*analysis
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - Karyotyping
MH  - Male
MH  - Osteosarcoma/*genetics
MH  - Rhabdomyosarcoma/*genetics
MH  - Sarcoma, Ewing/*genetics
MH  - Tumor Cells, Cultured
EDAT- 1989/10/01 00:00
MHDA- 1989/10/01 00:01
CRDT- 1989/10/01 00:00
PHST- 1989/10/01 00:00 [pubmed]
PHST- 1989/10/01 00:01 [medline]
PHST- 1989/10/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1989 Oct 1;49(19):5407-13.