Alba-Pavón Piedad, Alaña Lide, Astigarraga Itziar, Villate Olatz
Pediatric Oncology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
Pediatric Service, Hospital Universitario Cruces, 48903 Barakaldo, Spain.
Cancers (Basel). 2022 Dec 2;14(23):5967. doi: 10.3390/cancers14235967.
The prevalence of hereditary cancer in children was estimated to be very low until recent studies suggested that at least 10% of pediatric cancer patients carry a germline mutation in a cancer predisposition gene. A significant proportion of pathogenic variants associated with an increased risk of hereditary cancer are variants affecting splicing. RNA splicing is an essential process involved in different cellular processes such as proliferation, survival, and differentiation, and alterations in this pathway have been implicated in many human cancers. Hereditary cancer genes are highly susceptible to splicing mutations, and among them there are several genes that may contribute to pediatric solid tumors when mutated in the germline. In this review, we have focused on the analysis of germline splicing-disrupting mutations found in pediatric solid tumors, as the discovery of pathogenic splice variants in pediatric cancer is a growing field for the development of personalized therapies. Therapies developed to correct aberrant splicing in cancer are also discussed as well as the options to improve the diagnostic yield based on the increase in the knowledge in splicing.
直到最近的研究表明至少10%的儿童癌症患者携带癌症易感基因的种系突变，儿童遗传性癌症的患病率一直被估计为非常低。与遗传性癌症风险增加相关的很大一部分致病变异是影响剪接的变异。RNA剪接是一个涉及增殖、存活和分化等不同细胞过程的重要过程，该途径的改变与许多人类癌症有关。遗传性癌症基因对剪接突变高度敏感，其中有几个基因在种系中发生突变时可能导致儿童实体瘤。在本综述中，我们重点分析了在儿童实体瘤中发现的种系剪接破坏突变，因为在儿童癌症中发现致病性剪接变异是个性化治疗发展的一个不断发展的领域。还讨论了为纠正癌症中异常剪接而开发的疗法，以及基于剪接知识增加来提高诊断率的选择。
