title: 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.
authors.affiliation: From the Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA; and Division of Pediatric Hematology/Oncology, Department of Pediatrics and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
authors.forename: David
authors.initials: D
authors.lastname: Malkin
authors.affiliation: From the Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA; and Division of Pediatric Hematology/Oncology, Department of Pediatrics and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
authors.affiliation: From the Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA; and Division of Pediatric Hematology/Oncology, Department of Pediatrics and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
authors.forename: Kristin
authors.initials: K
authors.lastname: Zelley
authors.affiliation: From the Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA; and Division of Pediatric Hematology/Oncology, Department of Pediatrics and Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schiffman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D053487:DEAD-box RNA Helicases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics / Q000628:therapy; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000628:therapy*; D010235:Paraganglioma / Q000235:genetics / Q000628:therapy; D043244:Ribonuclease III / Q000235:genetics; D055815:Young Adult
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases