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BRAF(V600E)突变在福岛年轻人群的甲状腺癌中高度普遍:与切尔诺贝利地区不同的致癌特征。

BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl.

作者信息

Mitsutake Norisato, Fukushima Toshihiko, Matsuse Michiko, Rogounovitch Tatiana, Saenko Vladimir, Uchino Shinya, Ito Masahiro, Suzuki Keiji, Suzuki Shinichi, Yamashita Shunichi

机构信息

Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University.

Nagasaki University Research Centre for Genomic Instability and Carcinogenesis (NRGIC).

出版信息

Sci Rep. 2015 Nov 20;5:16976. doi: 10.1038/srep16976.

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 BRAF(V600E) 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, BRAF(V600E) 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 BRAF(V600E) 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.

摘要

福岛第一核电站事故后,针对事故发生时年龄在0至18岁的儿童的甲状腺超声筛查项目于2011年10月启动。该人群中甲状腺癌的患病率似乎非常高(每296,253人中有84例)。为了阐明发病机制,我们研究了这些肿瘤中驱动突变的存在情况。对61例经典型乳头状甲状腺癌(PTC)、2例滤泡状变异型PTC、4例筛状-桑葚状变异型PTC和1例低分化甲状腺癌进行了分析。我们在43例(63.2%)中检测到BRAF(V600E),6例(8.8%)中检测到RET/PTC1,1例(1.5%)中检测到RET/PTC3,4例(5.9%)中检测到ETV6/NTRK3。在经典型和滤泡状变异型PTC中,BRAF(V600E)与肿瘤较小显著相关。这种基因模式与切尔诺贝利事故后的PTC完全不同,表明这些癌症的病因不是辐射所致。这是第一项展示通过大规模筛查发现的甲状腺癌中癌基因谱的研究,这可能反映了日本年轻人群中所有散发性和潜伏性肿瘤的基因状态。据推测,BRAF(V600E)可能不会赋予儿童PTC生长优势,而且这些病例中的许多生长缓慢,这表明其他因素可能对儿童PTC的肿瘤进展很重要。

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