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Studies of the retinoblastoma gene in human sarcomas
P T Reissmann1, M A Simon, W H Lee
1Department of Medicine, UCLA School of Medicine.
Abstract:
The retinoblastoma susceptibility gene, (RB), is a tumor suppressor gene which, when deleted is associated with the development of retinoblastoma. The observation that children with heritable retinoblastoma frequently develop second malignancies, principally sarcomas, led to the detection of similar RB gene deletions in some osteosarcomas. We studied 44 unselected sarcomas from patients with no antecedent retinoblastoma to determine the prevalence and nature of RB gene alterations. DNA and RNA were extracted from fresh tumors and analysed by Southern and Northern blotting. Three of nine osteosarcomas and 4 of 29 soft-tissue sarcomas had deletions of the RB gene. Four of these were full-length, and three were partial deletions of the gene. RNA from 5 of the 7 deleted tumors was studied, and 4 cases completely lacked the RB transcript. Transcripts were found in 19 of 20 tumors with an apparently intact RB gene, and in all the normal tissues studied. An additional tumor lacked the RB transcript, but the gene appeared intact at the DNA level. In total, 8 of 38 sarcomas were found to have alterations of the RB gene. These data indicate that the RB gene is inactivated in a significant number of sarcomas unrelated to retinoblastoma, and that the potential role for the gene in the pathogenesis of human malignancy may not be limited to retinoblastoma.
Insights
The retinoblastoma susceptibility gene (RB) is often altered in sarcomas, not just retinoblastoma. This study found RB gene alterations in 8 of 38 sarcomas, suggesting its broader role in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The retinoblastoma susceptibility gene (RB) is a known tumor suppressor.
- RB gene deletions are linked to retinoblastoma and second malignancies in affected children.
- Previous findings suggested RB gene involvement in osteosarcomas.
Purpose of the Study:
- To investigate the prevalence and nature of RB gene alterations in unselected sarcomas.
- To determine if RB gene inactivation occurs in sarcomas unrelated to retinoblastoma.
Main Methods:
- DNA and RNA extraction from fresh tumor samples.
- Analysis using Southern and Northern blotting techniques.
- Assessment of RB gene deletions and transcript levels.
Main Results:
- RB gene deletions were identified in 3 of 9 osteosarcomas and 4 of 29 soft-tissue sarcomas.
- Five of seven tumors with RB deletions showed a complete lack of RB transcript.
- RB gene alterations were found in 8 out of 38 total sarcomas studied.
Conclusions:
- The RB gene is inactivated in a notable proportion of sarcomas independent of retinoblastoma.
- RB gene alterations may contribute to the pathogenesis of various human sarcomas.
- The role of the RB gene in human malignancy extends beyond retinoblastoma.