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Science. 2019 Mar 15;363(6432):1170-1175. doi: 10.1126/science.aaw3535.

The genomic landscape of pediatric cancers: Implications for diagnosis and treatment.

Author information

1
Department of Pediatrics, Division of Hematology and Oncology, University of California, San Francisco, CA 94158, USA. jbiegel@chla.usc.edu alejandro.sweet-cordero@ucsf.edu.
2
Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA. jbiegel@chla.usc.edu alejandro.sweet-cordero@ucsf.edu.

Abstract

The past decade has witnessed a major increase in our understanding of the genetic underpinnings of childhood cancer. Genomic sequencing studies have highlighted key differences between pediatric and adult cancers. Whereas many adult cancers are characterized by a high number of somatic mutations, pediatric cancers typically have few somatic mutations but a higher prevalence of germline alterations in cancer predisposition genes. Also noteworthy is the remarkable heterogeneity in the types of genetic alterations that likely drive the growth of pediatric cancers, including copy number alterations, gene fusions, enhancer hijacking events, and chromoplexy. Because most studies have genetically profiled pediatric cancers only at diagnosis, the mechanisms underlying tumor progression, therapy resistance, and metastasis remain poorly understood. We discuss evidence that points to a need for more integrative approaches aimed at identifying driver events in pediatric cancers at both diagnosis and relapse. We also provide an overview of key aspects of germline predisposition for cancer in this age group.

PMID:
30872516
DOI:
10.1126/science.aaw3535

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