An increase in the incidence of papillary thyroid cancer has been documented in individuals exposed to Chernobyl fallout in 1986. Experiments using cultured human cells have suggested that radiation can induce the ret/PTC1 rearrangement involving the ret proto-oncogene. To test the hypothesis that the ret/PTC1 rearrangement is involved in the pathogenesis of Chernobyl-associated papillary thyroid carcinomas, we studied a panel of 31 cases from Belarus. All individuals lived in fallout-contaminated oblasts (regions) of Belarus at the time of the accident: Gomel (n = 13), Brest (n = 12), Minsk (n = 4), and Grodno (n = 2). All were under age 20 at the time of the accident; 20 were born between 1982 and 1986. Individual thyroid radiation doses were estimated at 1.1 to 110 rem. Patients underwent surgery in Minsk in 1996. Fifteen patients had locally advanced disease (stage T4). The majority had regional lymph node involvement (stage N1, n = 27). There were no distant metastases. Surgical specimens were frozen at -80 degrees C, RNA was extracted and cDNA prepared. The polymerase chain reaction (PCR) was performed with specific primers for ret/PTC1, and c-ret and GAPDH as controls. Controls were positive in all 31 cases. Nine cases yielded a positive PCR product for the ret/PTC1 rearrangement (29%). Thus, the ret/PTC1 rearrangement is a feature of some Chernobyl-associated papillary thyroid cancers, and is one possible mechanism involved in the pathogenesis of these cancers.
After the Chernobyl accident in 1986, there was a significant increase in the incidence of papillary thyroid cancer in fallout-exposed children from Belarus. Radiation-induced rearrangements of chromosome 10 involving the c-ret proto-oncogene have been implicated in the pathogenesis of these cancers. The ret/PTC3r1 rearrangement was the most prevalent molecular lesion identified in post-Chernobyl papillary thyroid cancers arising in 1991 and 1992. We identified the ret/PTC1 rearrangement in 29% of 31 papillary thyroid cancers presenting in Belarus in 1996. In the present report, we examined 14 cases from this series (plus 1 additional case) and found a ret/PTC3r1 rearrangement in only 1 (7%). The prevalence of ret/PTC3r1 in this series is significantly lower than previously reported (p = 0.0006, Fisher exact test). This result suggests a switch in the ratio of ret/PTC3 to ret/PTC1 rearrangements in late (1996) versus early (1991-1992) post-Chernobyl papillary thyroid cancers.
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