Comment[ArrayExpressAccession]	E-GEOD-16724
Investigation Title	Rearrangement of CRLF2 in B-progenitor and Down syndrome associated acute lymphoblastic leukemia
Comment[Submitted Name]	Rearrangement of CRLF2 in B-progenitor and Down syndrome associated acute lymphoblastic leukemia
Publication Title	Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia.
Publication Author List	Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J, Ma J, Coustan-Smith E, Harvey RC, Willman CL, Mikhail FM, Meyer J, Carroll AJ, Williams RT, Cheng J, Heerema NA, Basso G, Pession A, Pui CH, Raimondi SC, Hunger SP, Downing JR, Carroll WL, Rabin KR
Publication DOI	
PubMed ID	19838194
Experimental Design	comparative genomic hybridization by array
Experimental Design Term Source REF	EFO
Public Release Date	2009-10-18
Experiment Description	Chromosomal aneuploidy and translocations are hallmarks of acute lymphoblastic leukemia (ALL), but many patients lack a recurring chromosomal alteration. Here we report a recurring interstitial deletion of the pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that results in the expression of a novel fusion that juxtaposes the first non-coding exon of P2RY8 to the coding region of the CRLF2  (cytokine receptor like factor 2, or thymic stromal lymphopoietin receptor) gene. The P2RY8-CRLF2 fusion was identified in 7% of B-ALL cases, and was very common in ALL associated with Down syndrome (55% of cases) and was associated with the presence of JAK mutations. The P2RY8-CRLF2 fusion results in increased expression of CRLF2, a lymphoid signaling molecule that forms a heterodimeric complex with interleukin receptor 7 alpha. These findings identify a novel recurring chromosomal alteration in B-ALL, and suggest that perturbed CRLF2-mediated signaling is a key event in leukemogenesis in these cases. Profiling of tumor acquired DNA copy number alterations in 2 patients with Down syndrome associated B-progenitor acute lymphoblastic leukemia. Matched tumor and normal DNA was used for each array hybridization in each case.								
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Term Source Name	EFO
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Person Last Name	Mullighan	Mullighan							
Person First Name	Charles	Charles							
Person Mid Initials	G	G							
Person Email	charles.mullighan@stjude.org								
Person Affiliation	St Jude Children's Research Hospital								
Person Phone	1-901-595-3387								
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Person Address	Pathology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA								
Person Roles	submitter								
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Protocol Name	P-GSE16724-1	P-GSE16724-7	P-GSE16724-8	P-GSE16724-6	P-GSE16724-4	P-GSE16724-2	P-GSE16724-3	P-GSE16724-5	P-GSE16724-9
Protocol Description	ID_REF = <br>VALUE = LOWESS normalized Log2Ratio (tumor/normal)	Scanned on an Agilent C2565CA scanner.	Images were quantified using Agilent Feature Extraction Software (version 10.5.1.1).	Hybridization was carried out in an Agilent oven at 65°C for 40 hours at 20 rpm, followed by standard wash procedures	Ultra high molecular weight DNA was extracted by column based methods (DNA blood mini kit, Qiagen, Valencia, CA) or phenol-chloroform extraction	Ficoll enriched, cryopreserved cells were obtained at time of diagnosis of acute lymphoblastic leukemia, and at the time of remission	Samples were over 90% tumor cells (blasts) for the tumor samples, and <1% tumor cells for the remission samples	genomic DNA was labeled using the Agilent’s ULS Labeling kit	Linear Models for Microarray Analysis was implemented in Bioconductor  was used for background subtraction and LOWESS normalization.
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Protocol Type	bioassay_data_transformation	image_aquisition	image_aquisition	hybridization	nucleic_acid_extraction	grow	grow	labeling	feature_extraction
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Experimental Factor Name	SAMPLE								
Experimental Factor Type	sample								
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Comment[SecondaryAccession]	GSE16724								
Comment[GEOLastUpdateDate]	2010-01-19
Comment[GEOReleaseDate]	2009-10-17
Comment[ArrayExpressSubmissionDate]	2009-06-18
SDRF File	E-GEOD-16724.sdrf.txt