Nussinov Ruth, Yavuz Bengi Ruken, Demirel Habibe Cansu, Arici M Kaan, Jang Hyunbum, Tuncbag Nurcan
Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Cancer Innovation Laboratory, National Cancer Institute, Frederick, MD, United States.
Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.
Front Cell Dev Biol. 2024 Jul 2;12:1376639. doi: 10.3389/fcell.2024.1376639. eCollection 2024.
The connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do individuals with neurodevelopmental disorders, such as autism and schizophrenia, face higher chances of cancer emerging throughout their lifetime? Our broad review emphasizes the multi-scale aspect of this type of reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at the new understanding that can be gained. Within this framework, our review calls attention to computational strategies which can be powerful in discovering connections, causalities, predicting clinical outcomes, and are vital for drug discovery. Thus, rather than centering on the clinical features, we draw on the rapidly increasing data on the molecular level, including mutations, isoforms, three-dimensional structures, and expression levels of the respective disease-associated genes. Their integrated analysis, together with chromatin states, can delineate how, despite being connected, neurodevelopmental disorders and cancer differ, and how the same mutations can lead to different clinical symptoms. Here, we seek to uncover the emerging connection between cancer, including pediatric tumors, and neurodevelopmental disorders, and the tantalizing questions that this connection raises.
癌症与神经发育障碍之间的联系及因果关系一直令人困惑。相同的细胞通路、蛋白质和突变怎么会导致临床表现差异巨大的病症呢？而且为什么患有神经发育障碍（如自闭症和精神分裂症）的个体在其一生中患癌症的几率更高呢？我们的全面综述强调了这类推理的多尺度方面。正如这些例子所示，我们的目标不是专注于特定的器官系统或疾病，而是旨在获得新的认识。在此框架内，我们的综述提请人们注意计算策略，这些策略在发现联系、因果关系、预测临床结果方面可能很强大，并且对药物发现至关重要。因此，我们不是以临床特征为中心，而是利用分子水平上迅速增加的数据，包括各自疾病相关基因的突变、异构体、三维结构和表达水平。它们与染色质状态的综合分析，可以描绘出尽管存在关联，但神经发育障碍和癌症是如何不同的，以及相同的突变如何导致不同的临床症状。在这里，我们试图揭示癌症（包括儿童肿瘤）与神经发育障碍之间新出现的联系，以及这种联系引发的诱人问题。
