Malkin David, Nichols Kim E, Zelley Kristin, Schiffman Joshua D
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.
Am Soc Clin Oncol Educ Book. 2014:e44-55. doi: 10.14694/EdBook_AM.2014.34.e44.
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.
我们对儿童、青少年和青年遗传性癌症综合征的认识不断加深。此外，我们现在认识到，在每种特定的癌症易感综合征中，包括血液系统恶性肿瘤的风险，肿瘤谱存在广泛差异。对这些综合征的基因突变、生物学后果、肿瘤风险和临床管理的进一步了解将改善患者的预后。在本文中，我们阐述了这些疾病在儿童和成人中发生的分子机制的多样性，重点关注李-弗劳梅尼综合征、遗传性副神经节瘤综合征、DICER1综合征和多发性内分泌肿瘤综合征。接下来将详细讨论儿科人群中可能发生的成人期肿瘤，包括基底细胞癌、结直肠癌、甲状腺髓样癌和肾上腺皮质癌，以及这些肿瘤可能提示的潜在遗传性癌症综合征。最后，探讨白血病易感综合征这一主题，特别关注与白血病风险相关的不同类型综合征（遗传不稳定性/DNA修复综合征、细胞周期/分化、骨髓衰竭综合征、端粒维持、免疫缺陷综合征以及转录因子/纯家族性白血病综合征）。在本文中，特别关注这些综合征的临床识别、基因检测以及通过早期肿瘤监测和筛查进行管理。
