Mutational analysis of the NF1 GAP-related domain in neuroectodermal tumors
Journal Article
·
· American Journal of Human Genetics
OSTI ID:133593
- Universita di Padova (Italy); and others
To try to contribute to the more precise characterization of the function of the NF1 gene in tumorigenesis we have analyzed the most conserved region of its coding sequence, the GAP-related domain (NF1 GRD), which is attributed with tumor suppressor function. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region, in situations such as tumors of neuroepithelial tissues. In these situations, the activity of the NF1 gene product, neurofibromis, a GTPase activating protein, seems to be crucial in regulating the mechanisms of signal transduction mediated by p21 ras. We have studied the NF1 GRD region by PCR amplification of each exon (exons 21-27a) followed by subsequent PAGE and SSCP analysis of the amplification products in 60 primary sporadic neuroectodermal tumors. Our sample included: 14 neuroblastoma, 11 glioblastoma, 8 medulloblastoma, 7 ependimoma, 6 peripheral PNET, 1 ganglioneuroma, 1 glioma, 1 Ewing sarcoma, 1 meningioma and 1 schwannoma. We have not identified structural alterations of the NF1 GRD region in the tumors analysed, with one possible exception now in the process of being characterized. We can conclude that the loss of the NF1 gene tumor suppressor function that might lead or contribute to the development of malignancies in tissues of neuroectodermal origin is not due to structural abnormalities of the region of the gene interacting with p21 ras, either as a negative regulator or as a downstream effector of it. These data, together with the observation that the oncogene ras 21 is not typically mutated in neuroectodermal tumors, and that GTP-ras has been found normally regulated in neurofibromis-deficient melanoma and neuroblastoma cell lines, seem to support the hypothesis that the antioncogene activity of the NF1 gene could be totally independent from its interaction with ras.
- OSTI ID:
- 133593
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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