The study of NF1 and p53 gene expression in NF-1 related neurofibroma
| Autor: | Yu-Chieh Chien, 簡玉潔 |
|---|---|
| Rok vydání: | 2007 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 95 Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic diseases. It has a high prevalence of approximately 1 in 4000-5000 and has been proved was caused by defects on the NF1 gene. The gene product of NF1 is named neurofibromin, containing a GRD (GAP-related domain) domain which can negatively modulate Ras pathway. The clinical expression and severity of NF1 patients is diverse, even within families. The penetrance of NF1 is close to 100%, and approximately 50% of cases carry spontaneous mutations. Nearly all NF1 patients eventually develop neurofibromas, and malignant transformation of neurofibromas may form malignant peripheral nerve sheath tumor (MPNST) which occurs in about 2% of NF1 patients. Previous studies of NF1-related MPNST have found p53 inactivation by mutation or other defects of cell cycle regulators which can affect p53 activity. These results indicate that p53 may participate in the tumorigenesis from neurofibromas to MPNST and raise our interest in the role of p53 in NF1-related neurofibroma. We investigate the NF1 and p53 gene expression from genomic level to protein level in NF1-related neurofibromas. We perform MLPA (multiplex ligation-dependent probe amplification) analysis assay on genomic DNA, quantitative real-time PCR technique on the mRNA, and combined immunohistochemistry method to evaluate the protein expression of NF1 and p53 gene in neurofibromas. The results of MLPA analysis showed 14 (51.85%) tumors with single or multiple NF1 exon deletion and 2 (7.4%) cases with single exon deletion of p53 gene in total of 27 tumor samples from 26 NF1 patients. The down-regulated expression of NF1 mRNA was found in 16 samples of 28 neurofibrmas (57.14%). Up-regulated expression of p53 mRNA was observed in 21 samples of 28 neurofibromas (75%). The higher immunoreactivity of p53 protein expression was obeserved in 7/12 (58.33%) ill-defined neurofibromas, and in 4/11 (36.36%) well-defined neurofibromas. This result implicated possible correlations of the p53 protein expression with the phenotype of neurofibromas. In summary, we proposed that p53 may interplay with NF1 but not directly in the NF1-related neurofibroma formation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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