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Mutation analysis of the c-mos proto-oncogene in human ovarian teratomas
K A de Foy1, S A Gayther, W H Colledge
1CRC Human Cancer Genetics Research Group, Addenbrooke's Hospital, Cambridge, UK.
Abstract:
Female transgenic mice lacking a functional c-mos proto-oncogene develop ovarian teratomas, indicating that c-mos may behave as a tumour-suppressor gene for this type of tumour. We have analysed the entire coding region of the c-MOS gene in a series of human ovarian teratomas to determine whether there are any cancer-causing alterations. DNA from twenty teratomas was analysed by single-strand conformational analysis (SSCA) and heteroduplex analysis (HA) to screen for somatic and germline mutations. In nine of these tumours the entire gene was also sequenced. A previously reported polymorphism and a single new sequence variant were identified, neither of which we would predict to be disease-causing alterations. These results suggest that mutations in the coding region of the c-MOS gene do not play a significant role in the genesis of human ovarian teratomas.
Insights
The c-MOS gene, initially suspected as a tumor suppressor, was analyzed in human ovarian teratomas. No disease-causing mutations were found, suggesting it does not play a significant role in these tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The c-MOS proto-oncogene's role in tumorigenesis is unclear.
- Transgenic mice lacking c-MOS develop ovarian teratomas, suggesting a tumor-suppressor function.
- Ovarian teratomas are germ cell tumors with diverse histological components.
Purpose of the Study:
- To investigate the c-MOS gene's coding region for cancer-causing alterations in human ovarian teratomas.
- To determine if somatic or germline mutations in c-MOS contribute to ovarian teratoma development.
Main Methods:
- Analysis of the entire coding region of the c-MOS gene in 20 human ovarian teratomas.
- Screening for mutations using single-strand conformational analysis (SSCA) and heteroduplex analysis (HA).
- Direct sequencing of the c-MOS gene in nine selected tumors.
Main Results:
- A previously reported polymorphism and one new sequence variant were identified in the c-MOS gene.
- These identified variants were not predicted to be disease-causing alterations.
- No significant somatic or germline mutations were detected in the c-MOS coding region.
Conclusions:
- Mutations within the coding region of the c-MOS gene are unlikely to be a major factor in the development of human ovarian teratomas.
- The tumor-suppressor role suggested by mouse models may not translate to human ovarian teratomas.
- Further research into other genetic or epigenetic factors is warranted for ovarian teratoma genesis.