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| Status |
Public on Mar 16, 2015 |
| Title |
SMO variants explain the majority of drug resistance in basal cell carcinoma [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms, providing a unique opportunity to study human tumor evolution. Here, we identify SMO mutations in 50% (22/44) of resistant BCCs compared with 5.6% (2/36) of untreated BCCs (p<0.0001), and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket (LBP) mutations that define sites of inhibitor binding and four variants that confer constitutive activity and inhibitor resistance, thus defining pivotal residues of SMO that ensure receptor autoinhibition. Finally, we show that both classes of SMO variants respond to the aPKC-ι/λ inhibitor PSI and GLI2 antagonist ATO that operate downstream of SMO
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| |
|
| Overall design |
Genome-wide gene expression profiling of 8 normal skin biopsies, 9 resistant basal cell cancers and 4 sensitive basal cell cancers.
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| |
|
| Contributor(s) |
Atwood SX, Sarin KY, Li J, Kim G, Rezaee M, Ally MS, Kim J, Yao C, Whitson RJ, Chang AS, Oro AE, Tang JY |
| Citation(s) |
25759020 |
| Submission date |
Jun 10, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Jiang Li |
| E-mail(s) |
jiangli@stanford.edu
|
| Phone |
6507258839
|
| Organization name |
Stanford University
|
| Department |
Dermatology
|
| Lab |
Tony Oro
|
| Street address |
269 Campus Drive, Stanford University
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (21)
|
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| This SubSeries is part of SuperSeries: |
| GSE58377 |
SMO variants explain the majority of drug resistance in basal cell carcinoma |
|
| Relations |
| BioProject |
PRJNA252377 |
| SRA |
SRP043085 |
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