Vellichirammal Neetha Nanoth, Chaturvedi Nagendra K, Joshi Shantaram S, Coulter Donald W, Guda Chittibabu
Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Pediatrics, Hematology, and Oncology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Cancer Lett. 2021 Feb 28;499:24-38. doi: 10.1016/j.canlet.2020.11.015. Epub 2020 Nov 25.
The incidence of pediatric cancers is rising steadily across the world, along with the challenges in understanding the molecular mechanisms and devising effective therapeutic strategies. Pediatric cancers are presented with diverse molecular characteristics and more distinct subtypes when compared to adult cancers. Recent studies on the genomic landscape of pediatric cancers using next-generation sequencing (NGS) approaches have redefined this field by providing better subtype characterization and novel actionable targets. Since early identification and personalized treatment strategies influence therapeutic outcomes, survival, and quality of life in pediatric cancer patients, the quest for actionable biomarkers is of great value in this field. Fusion genes that are prevalent and recurrent in several pediatric cancers are ideally suited in this context due to their disease-specific occurrence. In this review, we explore the current status of fusion genes in pediatric cancer subtypes and their use as biomarkers for diagnosis and personalized therapy. We discuss the technological advancements made in recent years in NGS sequencing and their impact on fusion detection algorithms that have revolutionized this field. Finally, we also discuss the advantages of pairing liquid biopsy protocols for fusion detection and their eventual use in diagnosis and treatment monitoring.
全球儿童癌症的发病率正在稳步上升,同时在理解分子机制和制定有效治疗策略方面也面临挑战。与成人癌症相比,儿童癌症具有多样的分子特征和更独特的亚型。最近使用下一代测序(NGS)方法对儿童癌症基因组格局的研究,通过提供更好的亚型特征描述和新的可操作靶点,重新定义了这一领域。由于早期识别和个性化治疗策略会影响儿童癌症患者的治疗效果、生存率和生活质量,因此寻找可操作的生物标志物在该领域具有重要价值。在几种儿童癌症中普遍且反复出现的融合基因,因其特定于疾病的发生情况,在这方面非常适用。在本综述中,我们探讨了融合基因在儿童癌症亚型中的现状及其作为诊断和个性化治疗生物标志物的应用。我们讨论了近年来NGS测序取得的技术进步及其对融合检测算法的影响,这些算法彻底改变了这一领域。最后,我们还讨论了将液体活检方案用于融合检测的优势及其最终在诊断和治疗监测中的应用。