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Updated: Aug 5, 2026
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Ras oncogene mutations in benign and malignant thyroid neoplasms
H Karga1, J K Lee, A L Vickery
1Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Abstract:
Current models for tumorigenesis propose that a series of genetic alterations occur during the progression from the normal cell to the malignant phenotype. Mutations in each of the three ras genes (K-ras, H-ras, and N-ras) have been identified in many human neoplasms, including thyroid cancer. In this study we examined genomic DNA from benign and malignant thyroid neoplasms for mutations that are known to activate the ras oncogenes (codons 12, 13, and 61). DNA from frozen surgically excised tissue (n = 8) and from formalin-fixed paraffin-embedded tissue (n = 30) was amplified by the polymerase chain reaction and screened for mutations using oligonucleotide-specific hybridization. No mutations were identified in follicular adenomas (n = 9). In follicular carcinomas, 2 of 14 tumors contained mutations (N-ras 61, Gln to Arg), and both of these patients had bone metastases. One of 15 papillary carcinomas had a ras mutation (H-ras 12, Gly to Ser). In contrast to other studies, we found that ras mutations are relatively uncommon in both benign and malignant thyroid neoplasms. Studies of larger numbers of tumors and comparisons of different patient populations will be required to assess a possible association of mutations in N-ras 61 with clinically aggressive follicular cancer.
Insights
Ras gene mutations are uncommon in thyroid neoplasms. This study found few mutations in benign and malignant thyroid tumors, suggesting further research is needed to link N-ras 61 mutations to aggressive follicular cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumorigenesis involves genetic alterations.
- Ras gene mutations are implicated in various human cancers, including thyroid cancer.
Purpose of the Study:
- To investigate the frequency of activating ras oncogene mutations (codons 12, 13, and 61) in benign and malignant thyroid neoplasms.
- To explore potential associations between ras mutations and clinical outcomes, such as bone metastases in follicular carcinoma.
Main Methods:
- Genomic DNA was extracted from thyroid tissue samples (n=38), including follicular adenomas, follicular carcinomas, and papillary carcinomas.
- DNA was amplified using the polymerase chain reaction (PCR).
- Mutations were screened using oligonucleotide-specific hybridization.
Main Results:
- No ras mutations were detected in follicular adenomas (n=9).
- Ras mutations were found in 2 of 14 follicular carcinomas (N-ras 61), both associated with bone metastases.
- One of 15 papillary carcinomas harbored a ras mutation (H-ras 12).
- Overall, ras mutations were relatively infrequent in the studied thyroid neoplasms.
Conclusions:
- Ras mutations appear to be uncommon in both benign and malignant thyroid neoplasms.
- The N-ras 61 mutation may be associated with aggressive follicular thyroid cancer, but larger studies are needed.
- Further research is required to confirm the role of ras mutations in thyroid cancer progression and clinical behavior.
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