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| Status |
Public on Dec 16, 2011 |
| Title |
Whole-exome sequencing identifies mutations of BCOR in acute myeloid leukemia with normal karyotype |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Among acute myeloid leukemias (AML) with normal karyotype (CN-AML), NPM1 and CEBPA mutations define WHO provisional entities accounting for ~60% of cases, but the remaining ~40% remains poorly characterized. By whole exome-sequencing (WES) of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3, MLL-PTD and IDH1, we newly identified a clonal somatic mutation in BCOR (BCL6 co-repressor), a gene located in chromosome X. Further analyses showed that BCOR mutations occurred in 11/262 (4.2%) CN-AML cases and represented a substantial fraction (14/82, 17.1%) of CN-AML patients showing the same genetic background as the index patient subjected to WES.
BCOR somatic mutations were: i) disruptive events similar to germline BCOR mutations causing the oculo-cranio-facial-dental (OCFD) genetic syndrome; ii) associated with markedly decreased BCOR mRNA levels, absence of full-length BCOR and absent or low expression of a truncated BCOR protein; iii) almost mutually exclusive with NPM1 mutations and frequently associated with DNMT3A and RUNX1 mutations, pointing to a cooperation between these events. Finally, BCOR mutations correlated with poor outcome among a cohort of 160 CN-AML patients (28% versus 66% overall survival at 2 yrs, P=0.024). Our results implicate for the first time BCOR in the pathogenesis of CN-AML without NPM1 mutations.
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| Overall design |
AML samples with normal karyotype were studied. Molecular analyses were performed for BCOR mutations. 12 BCOR wild-type cases and 12 BCOR mutated cases were hybridized to gene expression micro-arrays.
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| Contributor(s) |
Grossmann V, Tiacci E, Holmes A, Kohlmann A, Martelli MP, Kern W, Spanhol-Rosseto A, Klein H, Dugas M, Schindela S, Trifonov V, Schnittger S, Haferlach C, Bassan R, Wells VA, Spinelli O, Chan J, Rossi R, Baldoni S, De Carolis L, Goetze K, Serve H, Peceny R, Kreuzer K, Oruzio D, Specchia G, Di Raimondo F, Fabbiano F, Sborgia M, Liso A, Farinelli L, Rambaldi A, Pasqualucci L, Rabadan R, Haferlach T, Falini B |
| Citation(s) |
22012066 |
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| Submission date |
Jul 06, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Hans-Ulrich Klein |
| E-mail(s) |
h.klein@uni-muenster.de
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| Organization name |
Columbia University Medical Center
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| Department |
Neurology
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| Lab |
Center for Translational and Computational Neuroimmunology
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| Street address |
622 W 168th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA143515 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30442_RAW.tar |
109.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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