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| Status |
Public on Dec 22, 2013 |
| Title |
A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-kB signaling in chordoma biology [expression array] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R γ-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing.
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| Overall design |
Total five microarray experiments were conducted, two of which are for chordoma xenograft sammples and three for chrodoma primary tumor. RNA extracted from xenograft samples and from chordomas was hybridized to Illumina arrays.
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| Contributor(s) |
Meltzer P, Loeb D |
| Citation(s) |
24223206 |
| Submission date |
Aug 22, 2013 |
| Last update date |
Apr 09, 2014 |
| Contact name |
Yuelin Jack Zhu |
| E-mail(s) |
zhujack@mail.nih.gov
|
| Phone |
(240)760-7439
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| Organization name |
NCI
|
| Department |
Genetics Branch, Center for Cancer Research
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| Lab |
Dr. Paul Meltzer's Lab
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL6104 |
Illumina humanRef-8 v2.0 expression beadchip |
| GPL13376 |
Illumina HumanWG-6 v2.0 expression beadchip |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE50137 |
A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-kB signaling in chordoma biology |
|
| Relations |
| BioProject |
PRJNA216129 |
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