Brown Anna L, Churpek Jane E, Malcovati Luca, Döhner Hartmut, Godley Lucy A
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia; School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia.
Section of Hematology/Oncology, The University of Chicago Comprehensive Cancer Center, and the Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, USA.
Semin Hematol. 2017 Apr;54(2):60-68. doi: 10.1053/j.seminhematol.2016.11.003. Epub 2017 Apr 18.
Hereditary hematologic malignancy (HM) syndromes are increasingly recognized as causative of adult hematopoietic cancers, and the advent of next-generation sequencing has accelerated the discovery of new syndromes based on dense clustering of these diseases in particular families. Updated classifications schemes for myeloid malignancies will now include recommendations for taking a family history on all patients diagnosed with hematopoietic malignancies and for genetic counseling and testing of appropriate individuals and families. Therefore, now more than ever, clinicians and pathologists will need to have a high index of suspicion and be familiar with the aspects of a patient's personal or family history that should raise suspicion regarding these syndromes as well as the options for clinical testing. Whenever possible, individuals should be tested with certified, clinical platforms that can detect both point mutations and genomic rearrangements that disrupt gene function so that results are immediately actionable. Individuals and families who test negative for mutations in the known germline predisposition genes serve as important sources of discovery for new inherited susceptibility syndromes.
遗传性血液系统恶性肿瘤（HM）综合征越来越被认为是成人血液系统癌症的病因，下一代测序技术的出现加速了基于特定家族中这些疾病的密集聚集而发现新综合征的进程。现在，髓系恶性肿瘤的更新分类方案将包括对所有诊断为血液系统恶性肿瘤的患者进行家族史询问以及对合适的个体和家族进行遗传咨询和检测的建议。因此，现在临床医生和病理学家比以往任何时候都更需要保持高度警惕，并熟悉患者个人或家族史中应引起对这些综合征怀疑的方面以及临床检测的选择。只要有可能，就应该使用经过认证的临床平台对个体进行检测，这些平台能够检测破坏基因功能的点突变和基因组重排，以便检测结果能够立即用于指导治疗。在已知的种系易感基因中检测为突变阴性的个体和家族是发现新的遗传性易感性综合征的重要来源。
