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Updated: Feb 18, 2026
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
The genomic landscape of pediatric myelodysplastic syndromes
Jason R Schwartz1, Jing Ma2, Tamara Lamprecht2
1Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 260, Memphis, TN, 38105, USA.
Insights
Pediatric myelodysplastic syndromes (MDS) differ from adult MDS, with common Ras/MAPK pathway mutations and rare splicing gene mutations. Germline SAMD9/SAMD9L variants predispose children to MDS, often lost in tumor cells.
Area of Science:
- Genetics
- Pediatric Oncology
- Hematology
Background:
- Myelodysplastic syndromes (MDS) are rare in children and associated with poor outcomes.
- The genomic underpinnings of pediatric MDS are poorly understood compared to adult forms.
Purpose of the Study:
- To elucidate the somatic and germline genomic alterations in pediatric myelodysplastic syndromes.
- To compare the molecular landscape of pediatric MDS with adult MDS.
Main Methods:
- Whole exome sequencing, targeted amplicon sequencing, and RNA-sequencing were performed on 46 pediatric primary MDS patients.
- Somatic and germline genetic variations, including mutations and copy number alterations, were analyzed.
Main Results:
- Ras/MAPK pathway mutations were frequent (45%) in pediatric MDS, unlike adult MDS where splicing gene mutations are common.
- Mutations in RNA splicing genes were rare (2%) in the pediatric cohort.
- Germline variants in SAMD9 or SAMD9L were identified in 17% of patients and frequently lost in tumor cells via deletions (e.g., monosomy 7) or copy number neutral loss of heterozygosity (CN-LOH).
Conclusions:
- Pediatric and adult MDS represent distinct diseases with different underlying mechanisms.
- SAMD9/SAMD9L mutations define a novel category of MDS predisposition in children.
Abstract:
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.
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