Rare Tumors in Children: Progress Through Collaboration

Abstract

Rare pediatric tumors account for approximately 10% of all childhood cancers, which in themselves are a rare entity. The diverse histologies and clinical behaviors of rare pediatric tumors pose challenges to the investigation of their biologic and clinical features. National and international cooperative groups such as the Rare Tumor Committee of the Children's Oncology Group, Rare Tumors in Pediatric Age Project, and European Cooperative Study Group for Pediatric Rare Tumors have developed several initiatives to advance knowledge about rare pediatric cancers. However, these programs have been only partially effective, necessitating the development of alternative mechanisms to study these challenging diseases. In this article, we review the current national and international collaborative strategies to study rare pediatric cancers and alternative methods under exploration to enhance those efforts, such as independent registries and disease-specific, National Cancer Institute-sponsored clinics.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2015 by American Society of Clinical Oncology.

Figures

Fig 1.

Annual incidence of (A) malignancies and (B) carcinomas and melanomas in those age

Fig 2.

Classic adult-type GI stromal tumor (GIST; left) affects older patients, is CD117 positive by immunohistochemistry (IHC), and has KIT and PDGFR oncogenic mutations, resulting in ligand-independent kinase activation that contribute to tumor formation. These tumors are responsive to tyrosine kinase inhibitors (TKIs) such as imatinib. Succinate dehydrogenase (SDH) –deficient GIST (right) affects younger patients, is characterized by CD117 positivity by IHC, and IGF1R overexpression. These tumors are not responsive to TKIs and are characterized by loss of function of SDH complex; germline mutations of this complex are seen in > 50% of patients. Resultant succinate accumulation downregulates prolyl hydroxylase (PHD), leading to decreased proteasomal degradation and increased levels of hypoxia-inducible factor 1 (HIF1α). In addition, succinate accumulation leads to inhibition of 2-oxoglutarate–dependent dioxygenases, including ten-eleven translocation (TET) family of DNA-modifying enzymes and JmjC domain–containing histone lysine demethylases (KDM), resulting in dysregulated transcription and gene expression with consequent tumor formation.