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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Vydané v:	Nature communications Ročník 8; číslo 1; s. 1557 - 10
Hlavní autori:	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.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 16.11.2017 Nature Publishing Group Nature Portfolio
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-017-01590-5