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| Status |
Public on Dec 01, 2009 |
| Title |
PTEN and the PI3K/AKT Pathway in T-Cell Acute Lymphoblastic Leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
To comprehensively analyze the PTEN-PI3K-AKT pathway in T-ALL, we examined diagnostic DNA samples from a series of children with T-ALL by array CGH and sequence analysis, and identified genetic lesions in PTEN, PI3K or AKT in 47.7 % (n = 21 of 44) of cases. Furthermore, we identified a striking clustering of PTEN mutations in exon 7 in primary T-ALL patient samples, all of which encode mutations predicted to truncate the C2 domain without disrupting the phosphatase domain of PTEN. Induction chemotherapy failed in three of the four patients whose lymphoblasts harbored PTEN deletions at the time of diagnosis, while no induction failures occurred in the 12 cases with PTEN exon 7 mutations (P = 0.007), suggesting that PTEN deletion has more adverse therapeutic consequences than mutational disruptions that preserve the phosphatase domain. These findings provide a firm rationale for the development of therapies targeting the PI3K-AKT pathway in T-ALL.
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| Overall design |
We performed array-CGH with genomic DNAs from 47 pediatric T-ALL diagnostic specimens, 7 of which were reported in a previous publication. For the array-CGH, test DNA was always labeled by Cy3, and reference (pooled male DNA) - by Cy5. Single polarity hybridizations were performed, no dye-swap. Event-free survival was analyzed in the 44 pediatric T-ALL cases analyzed by both CGH and sequencing. Kaplan-Meier curves were generated using GraphPad Prism version 4.01, and differences between groups were compared by Gehan-Breslow-Wilcoxon Test.
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| Contributor(s) |
Gutierrez A, Sanda T, Grebliunaite R, Carracedo A, Salmena L, Ahn Y, Dahlberg S, Neuberg D, Moreau L, Winter S, Larson R, Zhang J, Protopopov A, Chin L, Pandolfi P, Silverman L, Hunger S, Sallan S, Look T |
| Citation(s) |
19458356, 20124220 |
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| Submission date |
Feb 23, 2009 |
| Last update date |
Oct 26, 2016 |
| Contact name |
Alexei Protopopov |
| Organization name |
UT MD Anderson Cancer Center
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| Department |
IACS
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| Street address |
1901 East Rd
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77054 |
| Country |
USA |
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| Platforms (1) |
| GPL4091 |
Agilent-014693 Human Genome CGH Microarray 244A (Feature number version) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA111831 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE14959_RAW.tar |
2.6 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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