Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 260, Memphis, TN, 38105, USA.
Department of Pathology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 342, Memphis, TN, 38105, USA.
Nat Commun. 2017 Nov 16;8(1):1557. doi: 10.1038/s41467-017-01590-5.
Myelodysplastic syndromes (MDS) are uncommon in children and have a poor prognosis. In contrast to adult MDS, little is known about the genomic landscape of pediatric MDS. Here, we describe the somatic and germline changes of pediatric MDS using whole exome sequencing, targeted amplicon sequencing, and/or RNA-sequencing of 46 pediatric primary MDS patients. Our data show that, in contrast to adult MDS, Ras/MAPK pathway mutations are common in pediatric MDS (45% of primary cohort), while mutations in RNA splicing genes are rare (2% of primary cohort). Surprisingly, germline variants in SAMD9 or SAMD9L were present in 17% of primary MDS patients, and these variants were routinely lost in the tumor cells by chromosomal deletions (e.g., monosomy 7) or copy number neutral loss of heterozygosity (CN-LOH). Our data confirm that adult and pediatric MDS are separate diseases with disparate mechanisms, and that SAMD9/SAMD9L mutations represent a new class of MDS predisposition.
骨髓增生异常综合征（MDS）在儿童中较为罕见，且预后不良。与成人 MDS 相比，人们对儿科 MDS 的基因组图谱知之甚少。在这里，我们使用全外显子测序、靶向扩增子测序和/或 46 名儿科原发性 MDS 患者的 RNA 测序，描述了儿科 MDS 的体细胞和种系变化。我们的数据表明，与成人 MDS 相比，Ras/MAPK 通路突变在儿科 MDS 中较为常见（原发性队列的 45%），而 RNA 剪接基因的突变则很少见（原发性队列的 2%）。令人惊讶的是，SAMD9 或 SAMD9L 的种系变异存在于 17%的原发性 MDS 患者中，这些变异通常通过染色体缺失（例如，单体 7）或拷贝数中性杂合性丢失（CN-LOH）在肿瘤细胞中丢失。我们的数据证实，成人和儿科 MDS 是两种具有不同机制的独立疾病，并且 SAMD9/SAMD9L 突变代表了一种新的 MDS 易感性类别。
