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Ras mutations are uncommon in sporadic thyroid cancer in children and young adults
C Fenton1, J Anderson, Y Lukes
1Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Abstract:
Mutations in the ras genes (H-ras, K-ras, and N-ras) occur in 10-15% of all human cancers, and commonly arise from single base substitutions at codons 12, 13, or 61. Although ras mutations have been found in adult thyroid cancers, they were absent from the two studies which examined childhood thyroid cancers. Both studies included only children with radiation induced thyroid cancer, and it remains unclear if ras mutations occur in children without radiation exposure. To answer this question, we examined archival tissue blocks from 31 children with papillary thyroid cancer (PTC) 4 with follicular thyroid cancer (FTC), 2 with medullary thyroid cancer (MTC), and 1 with lymphoma (LYM). Only 1 patient with PTC had previous radiation exposure. Genomic DNA was extracted and used for PCR amplification of the ras genes. The PCR products were analyzed by oligospecific hybridization for mutations at codons 12, 13, and 61. Two of the PTCs (6.5%) contained ras mutations. Both patients had class II disease and no history of previous radiation exposure. One patient subsequently developed bone and lung metastases. The patient with lymphoma also had a ras mutation (N-61), but ras mutations were absent from all FTC and MTC. These results suggest that ras mutations are uncommon in spontaneous childhood thyroid cancer, but occur with a frequency similar to that found in previous reports of adult differentiated thyroid cancers. The number of subjects was too small to determine if ras mutations are more common in patients with aggressive papillary thyroid cancer.
Insights
Ras gene mutations are uncommon in spontaneous childhood thyroid cancers, occurring at a rate similar to adult differentiated thyroid cancers. Further research is needed to determine if these mutations are more frequent in aggressive papillary thyroid cancer cases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ras gene mutations (H-ras, K-ras, N-ras) are implicated in 10-15% of human cancers, typically at codons 12, 13, or 61.
- While found in adult thyroid cancers, ras mutations were absent in prior studies of childhood thyroid cancers, which exclusively examined radiation-induced cases.
Purpose of the Study:
- To investigate the occurrence of ras gene mutations in childhood thyroid cancers unrelated to radiation exposure.
- To compare the frequency of ras mutations in pediatric thyroid cancers with that observed in adult thyroid cancers.
Main Methods:
- Archival tissue blocks from 31 pediatric papillary thyroid cancers (PTC), 4 follicular thyroid cancers (FTC), 2 medullary thyroid cancers (MTC), and 1 lymphoma (LYM) were analyzed.
- Genomic DNA was extracted for PCR amplification of ras genes, followed by oligospecific hybridization to detect mutations at codons 12, 13, and 61.
Main Results:
- Ras mutations were identified in 2 of 31 (6.5%) pediatric papillary thyroid cancers, both in patients without prior radiation exposure.
- One patient with papillary thyroid cancer and a ras mutation developed distant metastases. The lymphoma case also showed a ras mutation (N-61).
- No ras mutations were detected in follicular thyroid cancer or medullary thyroid cancer cases.
Conclusions:
- Ras mutations are infrequent in spontaneous childhood thyroid cancers but occur at a frequency comparable to adult differentiated thyroid cancers.
- The study's small sample size precludes definitive conclusions about the association between ras mutations and aggressive papillary thyroid cancer.