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Series GSE33315 Query DataSets for GSE33315
Status Public on Jan 10, 2012
Title Discovery of novel recurrent mutations and rearrangements in early T-cell precursor acute lymphoblastic leukaemia by whole genome sequencing
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Acute lymphoblastic leukaemia with early T-cell precursor immunophenotype (ETP ALL) is a highly aggressive subtype of ALL of unknown aetiology. To gain insights into the genetic basis of this disease, we performed whole genome sequencing of tumour and normal DNA of 12 children with ETP ALL. Analysis of structural and sequence variants in this discovery cohort, and mutation recurrence screening in a panel of 51 ETP and 43 non ETP ALL samples identified a high frequency of activating mutations in genes regulating cytokine receptor and Ras signalling, including IL7R, NRAS, KRAS, FLT3, BRAF, JAK1 and JAK3 in ETP ALL. Moreover, we identified multiple new targets of mutation in including GATA3, EP300, RUNX1, DNM2, ECT2L, HNRNPA1 and HNRNPR, as well as genes known to be mutated in T-ALL, including NOTCH1, PHF6, and WT1.. Five of 12 ETP ALL cases harboured novel chromosomal translocations, several of which accompanied complex multichromosomal rearrangements and resulted in the expression of chimeric in-frame fusion genes disrupting hematopoietic regulators, including ETV6-INO80D, NAP1L1-MLLT10 and RUNX1-EVX1. These results indicate that although ETP ALL is genetically heterogeneous, activation of Ras and cytokine receptor signalling distinguishes this disease from non-ETP ALL. These findings suggest that targeting this pathway may improve the currently dismal outcome of this disease.
Overall design Gene expression profiling of an extended panel of childhood B-lineage and T-lineage acute lymphoblastic leukemia samples was performed using Affymetrix U133A arrays.
Contributor(s) Mullighan C, Song G, Chen S, Shurtleff S, Campana D, Downing J
Citation(s) 22237106, 23733505
Submission date Oct 28, 2011
Last update date Nov 14, 2018
Contact name Charles G Mullighan
Phone 901-595-3387
Fax 901-595-5947
Organization name St. Jude Children's Research Hospital
Department Pathology
Lab Mullighan
Street address 262 Danny Thomas Place, MS 342
City Memphis
State/province TN
ZIP/Postal code 38105-3678
Country USA
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (575)
GSM705467 SJPHALL024
GSM705468 SJPHALL004
GSM705469 SJPHALL005
BioProject PRJNA149299

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
GSE33315_RAW.tar 1.5 Gb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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