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大脑和甲状腺瘤的转录组概况的差异与NTRK基因重排

A A Kechin^1,2, M A Koryukov^3,4, M A Smertina³

¹Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia. aa_kechin@niboch.nsc.ru.

Bulletin of experimental biology and medicine

|June 19, 2023

概括

大脑瘤和甲状腺癌中的NTRK基因重组改变了基因转录. 这项研究比较了NTRK重组与非重组瘤中的基因活性,揭示了特定基因和microRNA表达的显著差异.

科学领域:

基因组学和分子生物学
癌症研究癌症研究
文字转录学 (Transcriptomics) 是一个学科.

背景情况:

瘤发生可以由NTRK基因融合驱动,使这些变化成为Entrectinib和Larotrectinib等特定疗法的点.
了解NTRK基因重排的下游转录效应对于理解瘤生物学和识别潜在生物标志物至关重要.
大脑瘤 (BT) 和甲状腺癌 (TC) 代表了可以发生NTRK变化的不同实体,需要进行比较分析.

研究的目的:

为了比较NTRK重组 (NTRK+) 与非重组 (NTRK-) 脑瘤和甲状腺癌中的基因转录活性.
为了识别特定的基因和微RNAs (miRNAs),其表达因NTRK基因重组而改变.
调查NTRK+ BT和TC之间转录激活模式的潜在差异.

主要方法:

利用癌症基因组图集 (TCGA) 和基因表达总汇 (GEO) 数据库进行基因表达数据分析.
对脑瘤和甲状腺癌的NTRK+和NTRK-样本中基因的转录活性进行比较.
进行统计分析以确定观察到的基因和miRNA表达水平变化的意义.

主要成果:

与NTRK样本相比,在NTRK+样本中观察到JUN基因的转录增加 (1.6x为BT,2.5x为TC).
与NTRK-BT相比,在NTRK+BT中发现了八个HOX基因 (85-725倍增加) 的显著上调.
在NTRK+TC中检测到miR-31 (3x) 和miR-542 (2.5x) 的升高水平,而NTRK+BT显示miR-10b,miR-182和miR-21比NTRK-样本增加了5倍以上.

结论:

NTRK基因重组导致脑瘤和甲状腺癌中基因转录概况的明显改变.
特定的基因 (JUN,HOX) 和miRNAs (miR-31,miR-542,miR-10b,miR-182,miR-21) 在对NTRK变化的反应中被差异地表达.
这些发现强调了由NTRK重组驱动的分子异质性及其对瘤特异性基因表达的影响.

关键词:

俄罗斯国家广播电视台 (NTRK)大脑瘤是个大脑瘤质瘤质瘤是一种神经托芬受体的神经托芬受体甲状腺癌是一种癌症.

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