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| Status |
Public on Dec 06, 2007 |
| Title |
Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The aims of this study were to assess the feasibility of prospective pharmacogenomics research in multicenter international clinical trials of bortezomib in multiple myeloma and to develop predictive classifiers of response and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2 and phase 3 clinical trials of bortezomib and consented to genomic analyses of pretreatment tumor samples. Bone marrow aspirates were subject to a negative-selection procedure to enrich for tumor cells, and these samples were used for gene expression profiling using DNA microarrays. Data quality and correlations with trial outcomes were assessed by multiple groups. Gene expression in this dataset was consistent with data published from a single-center study of newly diagnosed multiple myeloma. Response and survival classifiers were developed and shown to be significantly associated with outcome via testing on independent data. The survival classifier improved on the risk stratification provided by the International Staging System. Predictive models and biologic correlates of response show some specificity for bortezomib rather than dexamethasone. Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents.
Keywords: Gene expression profiling; correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
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| Overall design |
Purified myeloma samples were collected prior to enrolment in clinical trials of bortezomib (PS-341). Samples were subject to replicate gene expression profiling using the Affymetrix 133A/B microarray. Data was normalized in MAS5.0 and the median of replicates is reported. Data was normalized to a Ttimmed mean of 15o and is NOT log transformed. Various patient parameters are reported as well as response, TTP and survival upon treatment with bortezomib or dexamethasone.
*** The authors have not submitted the CEL files for GSE9782. Thus, GSE9782 is incomplete.
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| Contributor(s) |
Bryant B, Mulligan G |
| Citation(s) |
17185464 |
| Submission date |
Dec 04, 2007 |
| Last update date |
Aug 10, 2018 |
| Contact name |
George Mulligan |
| Organization name |
Millennium Pharmaceuticals
|
| Department |
Clinical Development
|
| Street address |
35 Landsdowne Stree
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (2) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
| GPL97 |
[HG-U133B] Affymetrix Human Genome U133B Array |
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| Samples (528)
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| Relations |
| BioProject |
PRJNA103715 |
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