Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations.
Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations.
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DOI：
10.1002/cncr.29706
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发表时间：
2016-01-01
期刊：
影响因子：
6.2
通讯作者：
Maris JM
中科院分区：
文献类型：
--
作者：
Bosse KR;Maris JM
神经母细胞瘤是一种常见于幼儿的胚胎性恶性肿瘤，其恶性潜能具有显著的异质性。最近，神经母细胞瘤的遗传基础已经成为焦点，这不仅促进了对神经母细胞瘤肿瘤发生的更全面的理解，而且还揭示了新的致癌脆弱性，这些脆弱性正在被用于治疗。神经母细胞瘤是一种典型的儿科实体瘤，它使用复发性基因组改变，如高水平MYCN扩增，进行风险分层。考虑到在初次诊断时研究的原发性神经母细胞瘤肿瘤中复发性激活体细胞点突变或基因融合相对较少，将需要超越靶向突变或失调激酶的小分子的创新治疗方法，以实现患者总体生存率的显著改善。然而，复发性神经母细胞瘤中的克隆获得性致癌畸变目前正在被定义，并且可能提供一个通过针对复发性疾病中异常调节途径的分子靶向治疗来改善患者结局的机会。本文将总结神经母细胞瘤遗传学和基因组学的知识现状，突出了改善prostication和潜在的治疗机会，出现了从最近的进展，了解生殖系易感性，复发性节段性染色体改变，体细胞点突变和易位，克隆进化复发性神经母细胞瘤。
Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus, which has catalyzed not only a more comprehensive understanding of neuroblastoma tumorigenesis, but has also revealed novel oncogenic vulnerabilities that are being leveraged therapeutically. Neuroblastoma is a model pediatric solid tumor in its use of recurrent genomic alterations, such as high-level MYCN amplification, for risk stratification. Given the relative paucity of recurrent activating somatic point mutations or gene fusions in primary neuroblastoma tumors studied at initial diagnosis, innovative treatment approaches beyond small molecules targeting mutated or dysregulated kinases will be required moving forward to achieve noticeable improvements in overall patient survival. However, the clonally acquired, oncogenic aberrations in relapsed neuroblastomas are currently being defined and may offer an opportunity to improve patient outcomes with molecularly targeted therapy directed towards aberrantly regulated pathways in relapsed disease. This review will summarize the current state of knowledge of neuroblastoma genetics and genomics, highlighting the improved prognostication and potential therapeutic opportunities that have arisen from recent advances in understanding germline predisposition, recurrent segmental chromosomal alterations, somatic point mutations and translocations, and clonal evolution in relapsed neuroblastoma.