Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of childhood acute lymphoblastic leukemia ALL

ABSTRACT:

ORGANISM(S): Homo sapiens

SUBMITTER: Janos Demeter

PROVIDER: E-SMDB-2907 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles.

Subramanian Subbaya S West Robert B RB Corless Christopher L CL Ou Wenbin W Rubin Brian P BP Chu Kent-Man KM Leung Suet Yi SY Yuen Siu Tsan ST Zhu Shirley S Hernandez-Boussard Tina T Montgomery Kelli K Nielsen Torsten O TO Patel Rajiv M RM Goldblum John R JR Heinrich Michael C MC Fletcher Jonathan A JA van de Rijn Matt M

Oncogene 20041001 47

Most GISTs require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomic mechanisms of oncogene activation are heterogeneous. Notably, the kinase mutation type correlates with both tumor biology and imatinib response. For example, GISTs with KIT exon 11 mutations are typically gastric and have excellent imatinib response, whereas those with KIT exon 9 mutations generally arise in the small bowel and are less responsive to imatinib. To identify genes that mi ...[more]

PMID: 15326474

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Project description:We studied a cohort of 221 high-risk pediatric B-progenitor ALL patients that excluded known high risk ALL subtypes (BCR-ABL1 and infant ALL), using Affymetrix single nucleotide polymorphism microarrays, gene expression profiling and candidate gene resequencing. A CNA poor outcome predictor was identified using a semi-supervised principal components approach, and tested in an independent validation cohort of 258 pediatric B-progenitor ALL cases. Over 50 regions of recurring somatically acquired CNA, with the most frequently targeted genes encoding regulators of B-lymphoid development (66.8% of cases; with PAX5 targeted in 31.7% and IKZF1 in 28.6%). A CNA classifier identified a very poor outcome subgroup in the high-risk cohort (P=4.2x10-5) and was strongly associated with the presence of deletions involving IKZF1, which encodes the early lymphoid transcription factor IKAROS. This classifier, and IKZF1 deletions, also predicted poor outcome and elevated minimal residual disease at the end of induction therapy in the validation cohort. The gene expression signature of the poor outcome group was characterized by reduced expression of B lineage specific genes, and was highly related to the expressing signature of BCR-ABL1 ALL, a known high-risk ALL subtype also characterized by a high frequency of IKZF1 deletion.Somatically acquired deletions involving IKZF1 identify a very poor outcome subgroup of pediatric ALL patients. Incorporation of molecular tests to identify IKZF1 deletion in diagnostic leukemic blasts should improve the ability to accurately risk stratify patients for appropriate therapy. Affymetrix U133A arrays were performed according to the maufacturers directions on RNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. Samples with less than 80% blasts were flow sorted prior to RNA extraction Experiment Overall Design: One hundred seventy five pediatric B-progenitor ALL samples were studied using either Affymetrix U133A

Dataset Information

Transcription profiling of childhood acute lymphoblastic leukemia ALL

Publications

Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles.

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