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Series GSE21094 Query DataSets for GSE21094
Status Public on Jul 12, 2011
Title Genomic profiling in Down syndrome pediatric acute lymphoblastic leukemia
Organism Homo sapiens
Experiment type Expression profiling by array
Methylation profiling by array
SNP genotyping by SNP array
Genome variation profiling by SNP array
Summary Patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features. Whereas most DS-ALL cases lack the sentinel cytogenetic lesions that guide risk assignment in childhood ALL, JAK2 mutations and CRLF2 overexpression are highly enriched. To further characterize the unique biology of DS-ALL, we performed genome-wide profiling of 58 DS-ALL and 35 non-Down syndrome (NDS) ALL cases by DNA copy number, loss of heterozygosity, gene expression, and methylation analyses. We report novel deletions within the 6p22 histone gene cluster as significantly more frequent in DS-ALL, occurring in 12 DS (24%) and only a single NDS case (3%) (Fisher’s exact p = 0.013). Homozygous deletions yielded significantly lower histone expression levels, and were associated with higher methylation levels, distinct spatial localization of methylated promoters, and enrichment of highly methylated genes for specific pathways and transcription factor binding motifs. Gene expression profiling identified CRLF2 overexpression in nearly half DS-ALL cases, and supervised analysis identified an associated 39-gene signature. However, no expression signature was identified for DS-ALL overall, nor for histone status, suggesting that DS-ALL constitutes several, heterogeneous molecular entities. Characterization of pathways associated with histone deletions and high CRLF2 expression may identify opportunities for novel targeted interventions.

This SuperSeries is composed of the SubSeries listed below.
 
Overall design Refer to individual Series.
 
Contributor(s) Rabin KR, Loudin MG, Wang J, Leung HE, Gurusiddappa S, Meyer J, Condos G, Morrison D, Tsimelzon A, Devidas M, Heerema NA, Carroll AJ, Plon SE, Hunger SP, Basso G, Pession A, Bhojwani D, Carroll WL
Citation(s) 21647151
Submission date Mar 27, 2010
Last update date Mar 25, 2019
Contact name Hon-chiu Eastwood Leung
E-mail(s) exleung@txccc.org
Phone 832-824-4373
Fax 832-825-4038
URL http://www.txccc.org/content.cfm?content_id=1405
Organization name Baylor College of Medicine
Department Pediatrics
Lab Genomics and Proteomics Core Laboratory
Street address 1102 Bates Street Room C1030.09
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (3)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL6986 Illumina HumanCNV370-Duov1 DNA Analysis BeadChip (HumanCNV370v1)
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (233)
GSM521936 ALL_DS_177
GSM521937 ALL_DS_381
GSM521938 ALL_DS_459
This SuperSeries is composed of the following SubSeries:
GSE20872 Methylation data from Down syndrome and non-Down syndrome pediatric acute lymphoblastic leukemia cases and controls
GSE20910 Expression data from Down syndrome and non-Down syndrome pediatric acute lymphoblastic leukemia cases
GSE21091 SNP data from Down syndrome and non-Down syndrome pediatric acute lymphoblastic leukemia cases and controls
Relations
BioProject PRJNA126695

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21094_RAW.tar 352.5 Mb (http)(custom) TAR (of CEL, TXT)

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