Carroll William L, Raetz Elizabeth, Meyer Julia
From the Division of Pediatric Hematology/Oncology, Department of Pediatrics, NYU Langone Medical Center, New York, NY; Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY; Department of Pediatrics, University of Utah, Salt Lake City, UT; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Am Soc Clin Oncol Educ Book. 2015:e601-7. doi: 10.14694/EdBook_AM.2015.35.e601.
It is an exciting era in pediatric oncology with the advent of new technologies to comprehensively characterize cancer genomes in childhood tumors. Defining the genetic landscape of pediatric tumors has not only provided critical insight into tumor evolution, but it has also offered promise for more effective treatment in some cases, such as Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) and anaplastic lymphoma kinase (ALK)-mutated tumors. However, several challenges remain as the field of genomic tumor profiling emerges. This new technology is costly, and the overall impact on survival has yet to be determined. Tumor heterogeneity and clonal evolution have also presented challenges in the development of targeted therapy. In this article, we review breakthroughs in gene sequencing methodology and discuss examples where genomic discoveries have resulted in the recognition of tumor susceptibility as well as incorporation of targeted therapy. We also discuss how broad scale comprehensive tumor analyses have demonstrated the convergence of individual genetic alterations on common relevant pathways. Although the impact of tumor profiling is best studied within the context of rigorously designed clinical trials, there is promise that there will be growing opportunities for the adaption of precision medicine in pediatric oncology in the future.
随着用于全面刻画儿童肿瘤癌症基因组的新技术的出现，这是儿科肿瘤学中一个令人兴奋的时代。定义儿科肿瘤的遗传图谱不仅为肿瘤进化提供了关键见解，而且在某些情况下，如费城染色体阳性急性淋巴细胞白血病（ALL）和间变性淋巴瘤激酶（ALK）突变的肿瘤，也为更有效的治疗带来了希望。然而，随着基因组肿瘤分析领域的出现，仍存在一些挑战。这项新技术成本高昂，对生存率的总体影响尚未确定。肿瘤异质性和克隆进化在靶向治疗的发展中也带来了挑战。在本文中，我们回顾了基因测序方法的突破，并讨论了基因组发现导致肿瘤易感性的认识以及靶向治疗纳入的例子。我们还讨论了大规模综合肿瘤分析如何证明个体基因改变在共同相关途径上的汇聚。尽管肿瘤分析的影响最好在严格设计的临床试验背景下进行研究，但未来在儿科肿瘤学中应用精准医学的机会有望不断增加。
