Chetverina Darya, Vorobyeva Nadezhda E, Gyorffy Balazs, Shtil Alexander A, Erokhin Maksim
Group of Epigenetics, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov Street, Moscow 119334, Russia.
Group of Dynamics of Transcriptional Complexes, Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilov Street, Moscow 119334, Russia.
Cancers (Basel). 2023 Jun 3;15(11):3042. doi: 10.3390/cancers15113042.
The identification of mechanisms that underlie the biology of individual tumors is aimed at the development of personalized treatment strategies. Herein, we performed a comprehensive search of genes (termed Supertargets) vital for tumors of particular tissue origin. In so doing, we used the DepMap database portal that encompasses a broad panel of cell lines with individual genes knocked out by CRISPR/Cas9 technology. For each of the 27 tumor types, we revealed the top five genes whose deletion was lethal in the particular case, indicating both known and unknown Supertargets. Most importantly, the majority of Supertargets (41%) were represented by DNA-binding transcription factors. RNAseq data analysis demonstrated that a subset of Supertargets was deregulated in clinical tumor samples but not in the respective non-malignant tissues. These results point to transcriptional mechanisms as key regulators of cell survival in specific tumors. Targeted inactivation of these factors emerges as a straightforward approach to optimize therapeutic regimens.
确定个体肿瘤生物学背后的机制旨在开发个性化治疗策略。在此，我们对特定组织起源肿瘤至关重要的基因（称为超级靶点）进行了全面搜索。为此，我们使用了DepMap数据库门户，该门户包含通过CRISPR/Cas9技术敲除单个基因的广泛细胞系面板。对于27种肿瘤类型中的每一种，我们都揭示了在特定情况下缺失会致命的前五个基因，这表明了已知和未知的超级靶点。最重要的是，大多数超级靶点（41%）由DNA结合转录因子代表。RNAseq数据分析表明，一部分超级靶点在临床肿瘤样本中失调，但在相应的非恶性组织中未失调。这些结果表明转录机制是特定肿瘤细胞存活的关键调节因子。靶向灭活这些因子成为优化治疗方案的直接方法。
