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切尔诺贝利反应堆事故后儿童甲状腺乳头状癌中的NTRK1重排

NTRK1 re-arrangement in papillary thyroid carcinomas of children after the Chernobyl reactor accident.

作者信息

Beimfohr C, Klugbauer S, Demidchik E P, Lengfelder E, Rabes H M

机构信息

Institute of Pathology, Ludwig-Maximilians-University of Munich, Germany.

出版信息

Int J Cancer. 1999 Mar 15;80(6):842-7. doi: 10.1002/(sici)1097-0215(19990315)80:6<842::aid-ijc7>3.0.co;2-z.

Abstract

The prevalence of NTRK1 re-arrangement was determined in papillary thyroid carcinomas (PTCs) of children from Belarus who had been exposed to radioactive iodine after the Chernobyl reactor accident; 81 tumors were included, all of which were devoid of RET re-arrangement as analyzed in a current study on genomic alterations in PTC. Oncogenic fusion of the NTRK1 tyrosine kinase domain with the amino-terminal part of the tropomyosin gene (TPM3/NTRK1, trk) was observed in 5 tumors. A single tumor exhibited a TPR/NTRK1 fusion (TRK-T2). Reciprocal NTRK1/TPM3 transcripts were found in 4 of 5 tumors with TPM3/NTRK1 re-arrangement, indicating an intra-chromosomal balanced reciprocal inversion. No phenotypic differences from other post-Chernobyl childhood PTCs were detected. As compared with the high prevalence of RET re-arrangements reported for thyroid carcinomas of children after the Chernobyl reactor accident, NTRK1 re-arrangements appear rare. Our results confirm that activation of receptor tyrosine kinase genes plays the predominant role in post-Chernobyl childhood thyroid carcinogenesis.

摘要

对白俄罗斯儿童甲状腺乳头状癌(PTC)中NTRK1重排的患病率进行了测定,这些儿童在切尔诺贝利核反应堆事故后接触过放射性碘;共纳入81例肿瘤,在一项关于PTC基因组改变的当前研究中分析发现,所有肿瘤均无RET重排。在5例肿瘤中观察到NTRK1酪氨酸激酶结构域与原肌球蛋白基因(TPM3/NTRK1,trk)氨基末端部分发生致癌性融合。1例肿瘤表现为TPR/NTRK1融合(TRK-T2)。在5例发生TPM3/NTRK1重排的肿瘤中有4例发现了相互的NTRK1/TPM3转录本,表明存在染色体内平衡的相互倒位。未检测到与切尔诺贝利事故后其他儿童PTC有表型差异。与切尔诺贝利核反应堆事故后儿童甲状腺癌中报道的RET重排高患病率相比,NTRK1重排似乎很少见。我们的结果证实,受体酪氨酸激酶基因的激活在切尔诺贝利事故后儿童甲状腺癌发生中起主要作用。

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