Abstract
After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0–18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAFV600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAFV600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAFV600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.
Highlights
We obtained tissue samples from 68 patients operated at Fukushima Medical University, consisting of 61 classical papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly differentiated thyroid carcinoma (PDTC)
In samples without above-mentioned frequent known genetic alterations, we investigated the presence of AKAP9/BRAF and ETV6(exons 4 and 5)/NTRK3 rearrangements
We have demonstrated that high prevalence of the BRAFV600E mutation and low frequency of chromosomal rearrangements such as RET/PTC in young PTC cases were found by the screening program
Summary
Most of them were papillary thyroid carcinomas (PTCs) This increase has been thought to be due to screening effect with advances in diagnostic instruments in recent years, because the estimated thyroid doses of radioiodine exposure in Fukushima were far lower than those in Chernobyl[7,8,9], and the period from the date of the accident until the onset is too short. Regarding radiation-induced thyroid carcinomas, post-Chernobyl PTCs had higher prevalence of the RET/PTC rearrangements. In cases with short latency (developed less than 7–10 years after the accident), they were found in 64–86% of the tumours, and RET/PTC3 was the most frequent type of the rearrangement in this group[5].
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