Fisher Kevin E, Hsu Amy P, Williams Christopher L, Sayeed Hadi, Merritt Brian Y, Elghetany M Tarek, Holland Steven M, Bertuch Alison A, Gramatges Maria Monica
Department of Pathology & Immunology, and.
Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX; and.
Blood Adv. 2017 Feb 27;1(7):443-448. doi: 10.1182/bloodadvances.2016002311. eCollection 2017 Feb 28.
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line mutations regardless of family history or other clinical features associated with deficiency. In adults with familial -MDS, those with somatic mutations in experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric -MDS is unclear. Here, we studied a cohort of 8 pediatric patients with MDS and lacking additional -associated clinical features or significant family history and identified heterozygous germ line mutations in 5 patients, including 1 with a normal karyotype. For those with -MDS, we screened for somatic mutations in genes with prognostic relevance in AML/MDS, using a targeted next-generation sequencing panel. Although no somatic mutations in were observed, somatic mutations were found in , , , and One subject with deleterious mutations in , , and rapidly progressed to AML with disease that was refractory to treatment. Our findings confirm the importance of testing in primary pediatric MDS, even in the absence of other clinical features of GATA2 deficiency. Further, similar to what has been observed in adults with -MDS, somatic mutations with potential prognostic effect occur in children with MDS associated with mutations in .
大约10%的原发性骨髓增生异常综合征（MDS）患儿存在种系突变，这使得人们提议，对于所有原发性MDS患儿以及某些细胞遗传学表现（包括7号染色体单体）的患儿，无论其家族史或与GATA2缺乏相关的其他临床特征如何，都应进行种系突变检测。在患有家族性MDS的成人中，那些在GATA2中存在体细胞突变的患者疾病会迅速进展为急性髓系白血病（AML），且干细胞移植后的预后较差；然而，原发性小儿MDS中体细胞突变的发生率尚不清楚。在此，我们研究了一组8例患有MDS且无其他与GATA2相关临床特征或明显家族史的儿科患者，在5例患者中鉴定出杂合种系突变，其中1例核型正常。对于患有GATA2 - MDS的患者，我们使用靶向二代测序平台筛选了在AML/MDS中具有预后相关性的基因中的体细胞突变。虽然未观察到GATA2中的体细胞突变，但在NRAS、KRAS、FLT3和TET2中发现了体细胞突变。1例在NRAS、KRAS和TET2中存在有害突变的患者迅速进展为AML，且疾病难治。我们的研究结果证实了在原发性小儿MDS中进行GATA2检测的重要性，即使不存在GATA2缺乏的其他临床特征。此外，与在患有GATA2 - MDS的成人中观察到的情况类似，在与GATA2突变相关的MDS患儿中也会出现具有潜在预后影响的体细胞突变。
