The genomic landscape of pediatric myelodysplastic syndromes

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,...

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Published in:Nature communications Vol. 8; no. 1; pp. 1557 - 10
Main Authors: Schwartz, Jason R., Ma, Jing, Lamprecht, Tamara, Walsh, Michael, Wang, Shuoguo, Bryant, Victoria, Song, Guangchun, Wu, Gang, Easton, John, Kesserwan, Chimene, Nichols, Kim E., Mullighan, Charles G., Ribeiro, Raul C., Klco, Jeffery M.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 16.11.2017
Nature Publishing Group
Nature Portfolio
Subjects:
631/67/1990/1673
631/67/69
Adult
Animals
Cell Line
Child
Children
Cohort Studies
Copy number
Disorders
Gene sequencing
Genetic Predisposition to Disease - genetics
Genomics - methods
HEK293 Cells
Heterozygosity
Humanities and Social Sciences
Humans
Loss of Heterozygosity
MAP kinase
Mice
Monosomy
multidisciplinary
Mutation
Myelodysplastic syndrome
Myelodysplastic syndromes
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - pathology
Patients
Pediatrics
Proteins - genetics
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Splicing
Survival Analysis
Tumor cells
Tumor Suppressor Proteins - genetics
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Myelodysplastic syndromes (MDS) are uncommon in children and have poor prognosis. Here, the authors interrogate the genomic landscape of MDS, confirming adult and paediatric MDS are separate diseases with disparate mechanisms, and highlighting that SAMD9/SAMD9L mutations represent a new class of MDS predisposition.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01590-5