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白俄罗斯散发性儿童甲状腺乳头状癌的主要致癌驱动因素及其临床病理相关性

Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus.

作者信息

Rogounovitch Tatiana I, Mankovskaya Svetlana V, Fridman Mikhail V, Leonova Tatiana A, Kondratovitch Victor A, Konoplya Natalya E, Yamashita Shunichi, Mitsutake Norisato, Saenko Vladimir A

机构信息

Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan.

Institute of Physiology of the National Academy of Sciences of Belarus, 220072 Minsk, Belarus.

出版信息

Cancers (Basel). 2021 Jul 5;13(13):3374. doi: 10.3390/cancers13133374.

Abstract

Childhood papillary thyroid carcinoma (PTC) diagnosed after the Chernobyl accident in Belarus displayed a high frequency of gene rearrangements and low frequency of point mutations. Since 2001, only sporadic thyroid cancer occurs in children aged up to 14 years but its molecular characteristics have not been reported. Here, we determine the major oncogenic events in PTC from non-exposed Belarusian children and assess their clinicopathological correlations. Among the 34 tumors, 23 (67.6%) harbored one of the mutually exclusive oncogenes: 5 (14.7%) , 4 (11.8%) , 6 (17.6%) , 2 (5.9%) rare fusion genes, and 6 (17.6%) . No mutations in codons 12, 13, and 61 of , and , , or or were detected. Fusion genes were significantly more frequent than ( = 0.002). Clinicopathologically, was associated with solid growth pattern and higher tumor aggressiveness, and with classic papillary morphology and mild clinical phenotype, and with follicular-patterned PTC and reduced aggressiveness. The spectrum of driver mutations in sporadic childhood PTC in Belarus largely parallels that in Chernobyl PTC, yet the frequencies of some oncogenes may likely differ from those in the early-onset Chernobyl PTC; clinicopathological features correlate with the oncogene type.

摘要

白俄罗斯切尔诺贝利事故后诊断出的儿童乳头状甲状腺癌(PTC)显示出高频的基因重排和低频的点突变。自2001年以来,14岁及以下儿童仅发生散发性甲状腺癌,但其分子特征尚未见报道。在此,我们确定未接触辐射的白俄罗斯儿童PTC中的主要致癌事件,并评估它们与临床病理的相关性。在34例肿瘤中,23例(67.6%)含有一种相互排斥的致癌基因:5例(14.7%)为 ,4例(11.8%)为 ,6例(17.6%)为 ,2例(5.9%)为罕见融合基因,6例(17.6%)为 。未检测到 、 及 第12、13和61密码子, 、 或 或 的突变。融合基因比 更常见( = 0.002)。在临床病理方面, 与实体生长模式及更高的肿瘤侵袭性相关, 和 与经典乳头状形态及轻度临床表型相关, 与滤泡型PTC及侵袭性降低相关。白俄罗斯散发性儿童PTC中驱动突变谱在很大程度上与切尔诺贝利事故后PTC相似,但某些致癌基因的频率可能与早期发病的切尔诺贝利事故后PTC不同;临床病理特征与致癌基因类型相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f5/8268670/0813e98a6a42/cancers-13-03374-g001.jpg

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