Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Northwestern University, Chicago, IL.
Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX.
Am Soc Clin Oncol Educ Book. 2024 Jun;44(3):e432218. doi: 10.1200/EDBK_432218.
Although numerous barriers for clinical germline cancer predisposition testing exist, the increasing recognition of deleterious germline DNA variants contributing to myeloid malignancy risk is yielding steady improvements in referrals for testing and testing availability. Many germline predisposition alleles are common in populations, and the increasing number of recognized disorders makes inherited myeloid malignancy risk an entity worthy of consideration for all patients regardless of age at diagnosis. Germline testing is facilitated by obtaining DNA from cultured skin fibroblasts or hair bulbs, and cascade testing is easily performed via buccal swab, saliva, or blood. Increasingly as diagnostic criteria and clinical management guidelines include germline myeloid malignancy predisposition, insurance companies recognize the value of testing and provide coverage. Once an individual is recognized to have a deleterious germline variant that confers risk for myeloid malignancies, a personalized cancer surveillance plan can be developed that incorporates screening for other cancer risk outside of the hematopoietic system and/or other organ pathology. The future may also include monitoring the development of clonal hematopoiesis, which is common for many of these cancer risk disorders and/or inclusion of strategies to delay or prevent progression to overt myeloid malignancy. As research continues to identify new myeloid predisposition disorders, we may soon recommend testing for these conditions for all patients diagnosed with a myeloid predisposition condition.
尽管临床种系癌症易感性检测存在诸多障碍，但越来越多的认识到有害种系 DNA 变异会增加髓系恶性肿瘤的风险，这使得检测的转诊和检测的可及性稳步提高。许多种系易感性等位基因在人群中很常见，并且越来越多的已识别疾病使得遗传性髓系恶性肿瘤风险成为所有患者（无论诊断时的年龄如何）都值得考虑的实体。通过培养的皮肤成纤维细胞或毛囊获取 DNA 可以促进种系检测，并且通过颊拭子、唾液或血液很容易进行级联检测。随着诊断标准和临床管理指南越来越多地包括种系髓系恶性肿瘤易感性，保险公司认识到检测的价值并提供保险。一旦个体被识别出有害的种系变异，这种变异会增加髓系恶性肿瘤的风险，就可以制定个性化的癌症监测计划，该计划包括对造血系统以外的其他癌症风险进行筛查和/或其他器官病理学。未来还可能包括监测克隆性造血的发展，这种情况在许多种癌症风险疾病中很常见，或者包括延迟或预防向显性髓系恶性肿瘤进展的策略。随着研究继续识别新的髓系易感性疾病，我们可能很快会建议对所有诊断为髓系易感性疾病的患者进行这些疾病的检测。
