Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of CEBPA double-, single-mutant and CEBPA wild type AML


ABSTRACT: A previously predictive CEBPA double mutant (CEBPAdm) signature was hampered by the recently reported CEBPA silenced AML cases that carry a similar gene expression profile (GEP). Two independent AML cohorts were used to train and evaluate the predictive value of the CEBPAdm signature in terms of sensitivity and specificity. A predictive signature was created, containing 25-probe sets by using a logistic regression model with Lasso regularization, which selects discriminative probe sets between the classes, CEBPAdm and all other AML cases, CEBPA wild type (CEBPAwt) and CEBPA single mutant (CEBPAsm). Subsequently, a classifier was trained on the entire HOVON-SAKK cohort based on a two-class approach; CEBPAdm versus all other cases (CEBPAwt and CEBPAsm). This trained classifier subsequently classified 16 candidate CEBPAdm cases in the AMLSG-cohort out of 154 AML cases. This approach showed perfect sensitivity and specificity (both 100%). In addition, we have performed a classification between CEBPAdm ,CEBPAsm, and CEBPAwt to infer if we were able to accurately classify CEBPAsm cases. We observed that all CEBPAsm cases were classified as CEBPAwt, thus CEBPAsm cases do not have a consistent gene expression pattern and are different from the CEBPAdm group. All samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation. Routine diagnostic algorithms, including the characterization of molecular markers are performed.

ORGANISM(S): Homo sapiens

SUBMITTER: Erdogan Taskesen 

PROVIDER: E-GEOD-22845 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity.

Taskesen Erdogan E   Bullinger Lars L   Corbacioglu Andrea A   Sanders Mathijs A MA   Erpelinck Claudia A J CA   Wouters Bas J BJ   van der Poel-van de Luytgaarde Sonja C SC   Damm Frederik F   Krauter Jürgen J   Ganser Arnold A   Schlenk Richard F RF   Löwenberg Bob B   Delwel Ruud R   Döhner Hartmut H   Valk Peter J M PJ   Döhner Konstanze K  

Blood 20101221 8


We evaluated concurrent gene mutations, clinical outcome, and gene expression signatures of CCAAT/enhancer binding protein alpha (CEBPA) double mutations (CEBPA(dm)) versus single mutations (CEBPA(sm)) in 1182 cytogenetically normal acute myeloid leukemia (AML) patients (16-60 years of age). We identified 151 (12.8%) patients with CEBPA mutations (91 CEBPA(dm) and 60 CEBPA(sm)). The incidence of germline mutations was 7% (5 of 71), including 3 C-terminal mutations. CEBPA(dm) patients had a lower  ...[more]

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