Low Prevalence of the ret/PTC3r1 Rearrangement in a Series of Papillary Thyroid Carcinomas Presenting in Belarus Ten Years Post-Chernoby1

Abstract

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.

ret/PTC Activation Is Not Associated with Individual Radiation Dose Estimates in a Pilot Study of Neoplastic Thyroid Nodules Arising in Russian Children and Adults Exposed to Chernobyl Fallout

“…The rate of ret=PTC activation in the children in this study is clearly lower than the 84-87% activation rates detected in PTC cases arising following external beam irradiation (15,24,25), and may be lower than the 30-86% activation rates detected in PTCs developing after exposure to Chernobyl fallout during childhood that have been reported to date (3)(4)(5)(6)(7)(8)(9)(10)(11). However,…”

“…Analyses of radiation-associated PTC specimens usually find a higher rate of ret=PTC activation ranging from 30% to 86% (2). Even though ionizing radiation has been shown to induce ret=PTC rearrangements in thyroid cancer cell culture models, other variables such as ethnic background, age at diagnosis, and latency period between radiation exposure and development of clinically evident PTC may also have a significant impact on the prevalence rate of ret=PTC activation reported in clinical samples (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Preferential induction of RET/PTC1 rearrangement by X-ray irradiation

“…Also, no RET/ PTC2 was detected even when the amount of starting RNA used for RT ± PCR was increased by sixfold. Interestingly, recent observations have reported an increase in the frequency of RET/PTC1 in postChernobyl childhood PTC in comparison with previous reports (Pisarchik et al, 1998;Smida et al, 1999). Therefore, the high prevalence of RET/PTC3 may re¯ect radiation-associated PTC with short latency, whereas RET/PTC1 may be related with later occurring PTC.…”

BRAF Mutations are Uncommon in Papillary Thyroid Cancer of Young Patients

“…All of the PTC that had been examined for ras mutations (n ϭ 10) were negative for mutations in H-ras and N-ras. Among the 12 PTC that had been examined for ret/PTC mutations, 5 (42%) were negative, 3 contained the ret/PTC1 rearrangement (25%), 1 (8%) contained the ret/PTC2 rearrangement, 1 (8%) contained the ret/PTC3 rearrangement, 1 (8%) contained both ret/PTC1 and ret/PTC2 rearrangements, and 1 (8%) contained both ret/PTC1 and ret/PTC3 rearrangements (25)(26)(27)(28)(29)(30)(31)(32). Of note, the patient with both ret/PTC1 and ret/PTC3 rearrangements was the one patient known to have a history of radiation exposure.…”

“…Studies in adult PTC have shown an association of the BRAF T1796A mutation with more advanced stage of disease (19,20). Second, although we had previously analyzed many of these PTC for ret/PTC rearrangements and ras mutations, we only amplified the more common ras and ret/PTC mutations (ret/PTC1, ret/PTC2, and ret/PTC3) (25)(26)(27)(28)(29)(30)(31)(32). It is possible that some of these PTC might contain additional ret/PTC rearrangements, but we lack sufficient material to examine this possibility.…”