Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia.
Novosibirsk National Research State University, Novosibirsk, Russia.
Bull Exp Biol Med. 2023 May;175(1):78-85. doi: 10.1007/s10517-023-05815-0. Epub 2023 Jun 19.
For tumors with chimeric NTRK genes, entrectinib and larotrectinib can be prescribed regardless of tumor localization. We compared changes in the transcriptional activity of genes in brain tumors (BT) and thyroid cancer (TC) with rearrangement (NTRK+) and without rearrangement (NTRK-) of the NTRK genes using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We revealed an increase in the transcription of the JUN gene in NTRK+ samples in comparison with NTRK- samples: by 1.6 times for BT (p=0.239) and by 2.5 times for TC (p=0.003). The transcription of eight HOX genes in NTRK+ BT samples was also increased (by 85-725 times, p<0.05) in comparison with NTRK-. In NTRK+ TC samples, the level of miR-31 and miR-542 was statistically significantly higher (by 3 and 2.5 times, respectively) than in NTRK-samples. For the NTRK+ BT samples, the levels of miR-10b, miR-182, and miR-21 more than 5-fold surpassed the corresponding values in NTRK-samples (p<0.05). These findings reflect differences in activation of gene transcription resulting from NTRK gene rearrangement in BT and TC.
对于具有嵌合 NTRK 基因的肿瘤,可以根据肿瘤定位来规定恩曲替尼和拉罗替尼的使用。我们使用癌症基因组图谱 (TCGA) 和基因表达综合数据库 (GEO) 比较了具有 NTRK 基因重排 (NTRK+) 和没有重排 (NTRK-) 的脑肿瘤 (BT) 和甲状腺癌 (TC) 中基因转录活性的变化。与 NTRK-样本相比,我们发现 NTRK+样本中 JUN 基因的转录增加:BT 中增加 1.6 倍(p=0.239),TC 中增加 2.5 倍(p=0.003)。与 NTRK-相比,NTRK+ BT 样本中 8 个 HOX 基因的转录也增加了(增加 85-725 倍,p<0.05)。在 NTRK+ TC 样本中,miR-31 和 miR-542 的水平分别比 NTRK-样本高 3 倍和 2.5 倍(分别为 p<0.05)。对于 NTRK+ BT 样本,miR-10b、miR-182 和 miR-21 的水平超过 NTRK-样本的 5 倍(p<0.05)。这些发现反映了 NTRK 基因重排导致 BT 和 TC 中基因转录激活的差异。