Universal genetic testing for inherited susceptibility in children and adults with myelodysplastic syndrome and acute myeloid leukemia: are we there yet?
Universal genetic testing for inherited susceptibility in children and adults with myelodysplastic syndrome and acute myeloid leukemia: are we there yet?
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DOI：
10.1038/s41375-018-0051-y
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发表时间：
2018-07-01
期刊：
影响因子：
11.4
通讯作者：
Churpek, Jane E.
中科院分区：
文献类型：
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作者：
Tawana, Kiran;Drazer, Michael W.;Churpek, Jane E.
骨髓增生异常综合征（MDS）和急性髓性白血病（AML）病例的全面基因组分析使得能够检测和区分驱动和亚克隆突变，知情风险预测和明确的靶向治疗。这些对疾病生物学和管理的见解使多基因获得性突变检测成为散发性MDS和AML患者诊断评估的关键部分。最近，我们对越来越多的遗传因素在MDS/AML风险和管理中的作用的理解取得了迅速进展。认识到这一领域日益增长的影响，MDS和AML的临床指南和疾病分类系统最近将家族性MDS/AML易感综合征纳入其诊断算法。在这篇文章中，我们考虑了将遗传性MDS/AML基因检测纳入每个MDS/AML患者的前期分子诊断工作中所需克服的优点，缺点和障碍。对于已经进行基于小组的仅肿瘤检测的中心，包括与家族性MDS/AML相关的基因（例如，RUNX 1，CEBPA，GATA 2，TP 53），我们主张优化这些测试，以检测这些基因中的所有类型的种系变异，并转向前期配对肿瘤/种系测试，以最大限度地提高检测和简化患者护理。
Comprehensive genomic profiling of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cases have enabled the detection and differentiation of driver and subclonal mutations, informed risk prognostication, and defined targeted therapies. These insights into disease biology, and management have made multigene-acquired mutation testing a critical part of the diagnostic assessment of patients with sporadic MDS and AML. More recently, our understanding of the role of an increasing number of inherited genetic factors on MDS/AML risk and management has rapidly progressed. In recognition of the growing impact of this field, clinical guidelines and disease classification systems for both MDS and AML have recently incorporated familial MDS/AML predisposition syndromes into their diagnostic algorithms. In this perspective piece, we contemplate the advantages, disadvantages, and barriers that would need to be overcome to incorporate inherited MDS/AML genetic testing into the upfront molecular diagnostic work-up of every MDS/AML patient. For centers already performing panel-based tumor-only testing, including genes associated with familial forms of MDS/AML (e.g., RUNX1, CEBPA, GATA2, TP53), we advocate optimizing these tests to detect all types of germline variants in these genes and moving toward upfront paired tumor/germline testing to maximize detection and streamline patient care.