Ras mutations are uncommon in sporadic thyroid cancer in children and young adults

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 can cers, they were absent from the two studies which examined childhood thyroi d cancers. Both studies included only children with radiation induced thyro id cancer, and it remains unclear if ras mutations occur in children withou t radiation exposure. To answer this question, we examined archival tissue blocks from 31 children with papillary thyroid cancer (PTC) 4 with follicul ar thyroid cancer (FTC), 2 with medullary thyroid cancer (MTC), and 1 with lymphoma (LYM). Only 1 patient with PTC had previous radiation exposure. Ge nomic DNA was extracted and used for PCR amplification of the ras genes. Th e PCR products were analyzed by oligospecific hybridization for mutations a t codons 12, 13, and 61. Two of the PTCs (6.5%) contained ras mutations. Bo th patients had class II disease and no history of previous radiation expos ure. One patient subsequently developed bone and lung metastases. The patie nt with lymphoma also had a ras mutation (N-61), but ras mutations were abs ent from all FTC and MTC. These results suggest that ras mutations are unco mmon in spontaneous childhood thyroid cancer, but occur with a frequency si milar to that found in previous reports of adult differentiated thyroid can cers. The number of subjects was too small to determine if ras mutations ar e more common in patients with aggressive papillary thyroid cancer. (J. End ocrinol. invest. 22: 781-789, 1999) (C)1999, Editrice Kurtis.