Abstrate:
Ras proto-oncogenes are members of the superfamily of GTP-binding proteins. Many tyrosine kinase receptors, including those for epidermal growth factor, insulin, and nerve growth factor, signal through RAS proteins. The product of members of this oncogene family (H-, K-, N-ras) is a 21 kD protein with nucleotide binding activity, involved in the transduction of information from the cell surface to the nucleus. The three RAS proteins exit in two states: a resting state in which they are bound to GDP and an active state in which they bind GTP. The most common form of mutational activation of Ras oncogenes in human tumors is through single base substations affecting either the GTP-binding of main (codons 12 and 13) or the GTPase domain (codon 61) of the protein. Thus, mutant RAS proteins result in constitutive activation of the downstream signaling cascade because their affinity for GTP is increased or their GTPase activity is decreased, so that the protein cannot return to the resting state. To investigate we have screened 89 thyroid tumor specimens, which include 8 follicular carcinomas (FC), 42 papillary carcinoma (PTC), 2 anaplastic carcinoma (AC),5 Hurthle cell adenoma (HA), 12 follicular adenoma (FA) and 20 nodular goiter (NG), for mutation in three Ras genes using PCR and automatic sequencing. Four tumors contained Ras gene mutation. Of these, three were identified among FC (37.5%), which mutation were in the codon 61 of each Ras genes. One mutation were at codon 61 of N-ras in FA specimens (8.3%). In addition, 33.7% (30/89) of specimens contain H-ras codon 27 polymorphism. In conclusion, our data indicated that the prevalence rates of Ras gene mutation were 5.8% and 2.7% in thyroid carcinoma and thyroid benign adenoma, respectively. Other environmental or genetic factors might also involved in the thyroid tumorigenesis and worth further investigation. The data were further confirmed using the combination of the PCR and denaturing gradient gel electrophoresis (DGGE). Four more cases of possible Ras mutation were detected which did not revealed by automatic sequencing , indicating that DGGE is a more sensitive method in detecting single nucleotide mutation. DGGE analysis should increase the detection rate of Ras gene mutation in our analysis.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0926102-011452 |
| Date | 26 September 2002 |
| Creators | Chia-Yi, Hou |
| Contributors | Cheng Jiin-Tsuey, Liu Rue-Tsuan, Liu Jong-Kang |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0926102-011452 |
| Rights | unrestricted, Copyright information available at source archive |
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