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| Status |
Public on Dec 01, 2015 |
| Title |
Spitz tumors and melanomas with MET fusion |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
Oncogenic gene fusions have been identified in many cancers and many serve as biomarkers or targets for therapy. Here we identify six different melanocytic tumors with genomic rearrangements of MET fusing the kinase domain of MET in-frame to six different N-terminal partners. These tumors lack activating mutations in other established melanoma oncogenes. We functionally characterize two of the identified fusion proteins (TRIM4-MET and ZKSCAN1-MET) and find that they constitutively activate the mitogen-activated protein kinase (MAPK), phosphoinositol-3 kinase (PI3K), and phospholipase C gamma 1 (PLCĪ³1) pathways. The MET inhibitors cabozantinib (FDA-approved for progressive medullary thyroid cancer) and PF-04217903 block their activity at nanomolar concentrations. MET fusion kinases thus provide a potential therapeutic target for a rare subset of melanoma for which currently no targeted therapeutic options currently exist.
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| Overall design |
The UCSF dermatopathology array comparative genomic hybridizaton database consists of copy number profiles of difficult to classify tumors obtained in the course of clinical practice. These cases were noted to have either a copy number transition within MET with relative gain of the 3' end of the gene or gain of the distal portion of chromosome 7q. There are 6 cases in this series, with one replicate each.
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| Contributor(s) |
Yeh I, Bastian BC |
| Citation(s) |
26013381 |
| Submission date |
Apr 14, 2015 |
| Last update date |
May 17, 2016 |
| Contact name |
Iwei Yeh |
| E-mail(s) |
Iwei.Yeh@ucsf.edu
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| Organization name |
UCSF
|
| Department |
Dermatology
|
| Lab |
Bastian
|
| Street address |
1701 Divisadero St. Ste 280
|
| City |
San Francisco |
| State/province |
California |
| ZIP/Postal code |
94115 |
| Country |
USA |
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| Platforms (1) |
| GPL10123 |
Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA281056 |
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