Predisposition to Pediatric and Hematologic Cancers: A Moving Target

Abstract

Our understanding of hereditary cancer syndromes in children, adolescents, and young adults continues to grow. In addition, we now recognize the wide variation in tumor spectrum found within each specific cancer predisposition syndrome including the risk for hematologic malignancies. An increased understanding of the genetic mutations, biologic consequences, tumor risk, and clinical management of these syndromes will improve patient outcome. In this article, we illustrate the diversity of molecular mechanisms by which these disorders develop in both children and adults with a focus on Li-Fraumeni syndrome, hereditary paraganglioma syndrome, DICER1 syndrome, and multiple endocrine neoplasia syndrome. This is followed by a detailed discussion of adult-onset tumors that can occur in the pediatric population including basal cell carcinoma, colorectal cancer, medullary thyroid cancer, and adrenal cortical carcinoma, and the underlying hereditary cancer syndromes that these tumors could indicate. Finally, the topic of leukemia predisposition syndromes is explored with a specific focus on the different categories of syndromes associated with leukemia risk (genetic instability/DNA repair syndromes, cell cycle/differentiation, bone marrow failure syndromes, telomere maintenance, immunodeficiency syndromes, and transcription factors/pure familial leukemia syndromes). Throughout this article, special attention is made to clinical recognition of these syndromes, genetic testing, and management with early tumor surveillance and screening.KEY POINTSMany hereditary cancer syndromes can present in children and adults.Understanding the molecular basis of cancer predisposition syndromes will improve understanding of clinical presentation and management.Adult-onset tumors rarely present in childhood, but when they do, often represent an underlying genetic risk related to a hereditary cancer syndrome.Nearly 60 genes have been associated with different hereditary cancer syndromes that have varying risk for hematologic malignancies.Tumor surveillance will diagnose early tumors and improve clinical outcome in children and families recognized to have a hereditary cancer syndrome.