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| Status |
Public on Jul 06, 2010 |
| Title |
Whole-transcript expression data for soft-tissue sarcoma tumors and control normal fat specimens |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Soft tissue sarcomas are aggressive mesenchymal cancers that affect more than 10,600 new patients per year in the US, about 40% of whom will die of their disease. Soft tissue sarcomas exhibit remarkable histologic diversity, with more than 50 recognized subtypes, but our knowledge of their genomic alterations is limited. Here we describe the results of an integrative analysis of DNA sequence, copy number, and mRNA expression in 207 samples encompassing seven major subtypes. Genes mutated in more than 5% of samples within a subtype were KIT (in gastrointestinal stromal cell tumors, or GISTs), TP53 (pleomorphic liposarcomas), PIK3CA (myxoid/round-cell liposarcoma), and NF1 (both myxofibrosarcoma and pleomorphic liposarcoma). We show evidence that PIK3CA mutations, found in 18% of myxoid/round-cell liposarcomas, activate AKT in vivo and are associated with poor outcomes. Point mutations in the tumor suppressor gene NF1 were discovered in both myxofibrosarcomas and pleomorphic liposarcomas, while genomic deletions were observed in all subtypes at varying frequencies. Finally, we found that short hairpin RNA-based knockdown of a subset of genes that are amplified in dedifferentiated liposarcoma, including CDK4 and YEATS4, decreased cell proliferation. Our study yields the most detailed map of molecular alterations across diverse sarcoma subtypes to date and provides potential subtype-specific targets for therapy.
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| Overall design |
Human soft-tissue sarcoma specimens were profiled on Affymetrix U133A arrays per manufacturer's instructions.
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| Contributor(s) |
Taylor BS, Barretina J, Meyerson M, Singer S |
| Citation(s) |
20601955 |
| |
| Submission date |
Mar 30, 2010 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Barry Stephen Taylor |
| Organization name |
Memorial Sloan-Kettering Cancer Center
|
| Street address |
1275 York Avenue, Box #460
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (158)
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| This SubSeries is part of SuperSeries: |
| GSE21124 |
Subtype-specific genomic alterations define new targets for soft tissue sarcoma therapy |
|
| Relations |
| BioProject |
PRJNA129707 |
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