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| Status |
Public on Mar 16, 2015 |
| Title |
SMO variants explain the majority of drug resistance in basal cell carcinoma [Target Sequencing] |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| 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 |
Identification of Smo mutations in 30 resistant basal cell cancers and 36 untreated basal cell cancers
The exonic regions of PTCH1 and SMO were amplified using the Access Array platform (Fluidigm)
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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 |
| |
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| Platforms (1) |
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| Samples (66)
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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 |
PRJNA252375 |
| SRA |
SRP043088 |
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