Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clinic (HHMC).
Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clinic (HHMC).
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DOI：
10.1016/j.clml.2016.04.001
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Patel KP
中科院分区：
文献类型：
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作者：
DiNardo CD;Bannon SA;Routbort M;Franklin A;Mork M;Armanios M;Mace EM;Orange JS;Jeff-Eke M;Churpek JE;Takahashi K;Jorgensen JL;Garcia-Manero G;Kornblau S;Bertuch A;Cheung H;Bhalla K;Futreal A;Godley LA;Patel KP
尽管存在多种血液系统恶性肿瘤的易感因素，但大多数血液学家/肿瘤学家对遗传性癌症综合征(HCS)的评估并不理想。启动HCS评估的标准定义不明确，遗传性恶性血液病的基因检测结果也没有系统地报道。从2014年4月至2015年8月，67例患者被转诊到遗传性血液恶性肿瘤诊所(HHMC)。转介的原因包括(1)患者≤50年的骨髓衰竭或骨髓增生异常综合征，(2)在目标下一代测序面板上对已发现的RUNX1、GATA2或CEBPA突变的种系遗传进行评估，(3)强烈的个人和/或家族恶性肿瘤病史。所有恶性血液病患者均采用培养的皮肤成纤维细胞作为种系DNA。临床诊断为HCS 8例(12%)，RUNX1相关家族性血小板紊乱(FPD)/AML 4例，先天性角化不良、Fanconi贫血、种系DDX41和Li-Fraumeni综合征(LFS)各1例。两名分别关注FPD/AML和LFS的患者的RUNX1和TP53变异意义未知。此外，4名先前诊断为HCS的患者(1名LFS，3名FPD/AML)被转介进行进一步的评估和监测。在这组HHMC诊断的恶性血液病队列中，有12名患者(18%)确诊为HCS。HCS识别为改善和个体化治疗以及为家庭成员提供筛查/监测机会提供了洞察力。HHMC促进了HCS的诊断，并倡导随着临床对血液系统恶性肿瘤易感综合征认识的提高，可以确定更多可能从评估中受益的患者。用于预测的突变小组可能为生殖系测试提供更多的临床怀疑。
Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported. From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC). Referral reasons included (1) bone marrow failure or myelodysplastic syndrome in patients ≤50 years, (2) evaluation for germline inheritance of identified RUNX1, GATA2, or CEBPA mutations on targeted next-generation sequencing panels, (3) strong personal and/or family history of malignancy. Cultured skin fibroblasts were utilized for germline DNA in all patients with hematologic malignancy. Eight (12%) patients were clinically diagnosed with a HCS; 4 patients with RUNX1-related familial platelet disorder (FPD)/AML, and one patient each with dyskeratosis congenita, Fanconi anemia, germline DDX41, and Li-Fraumeni Syndrome (LFS). Two patients with concern for FPD/AML and LFS, respectively, had RUNX1 and TP53 variants of unknown significance. Additionally, four patients with prior HCS diagnosis (1 LFS, 3 FPD/AML) were referred for further evaluation and surveillance. In this HHMC-referred hematologic malignancy cohort, HCS was confirmed in twelve patients (18%). HCS identification provides insight for improved and individualized treatment, and screening/surveillance opportunities for family members. The HHMC has facilitated HCS diagnosis, and advocates that with increased clinical awareness of hematologic malignancy predisposition syndromes, more patients who may benefit from evaluation can be identified. Mutation panels intended for prognostication may provide increased clinical suspicion for germline testing.