| First Author | Molyneux SD | Year | 2010 |
| Journal | J Clin Invest | Volume | 120 |
| Issue | 9 | Pages | 3310-25 |
| PubMed ID | 20697156 | Mgi Jnum | J:165282 |
| Mgi Id | MGI:4836788 | Doi | 10.1172/JCI42391 |
| Citation | Molyneux SD, et al. (2010) Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. J Clin Invest 120(9):3310-25 |
| abstractText | Some cancers have been stratified into subclasses based on their unique involvement of specific signaling pathways. The mapping of human cancer genomes is revealing a vast number of somatic alterations; however, the identification of clinically relevant molecular tumor subclasses and their respective driver genes presents challenges. This information is key to developing more targeted and personalized cancer therapies. Here, we generate a new mouse model of genomically unstable osteosarcoma (OSA) that phenocopies the human disease. Integrative oncogenomics pinpointed cAMP-dependent protein kinase type I, alpha regulatory subunit (Prkar1a) gene deletions at 11qE1 as a recurrent genetic trait for a molecularly distinct subclass of mouse OSA featuring RANKL overexpression. Using mouse genetics, we established that Prkar1a is a bone tumor suppressor gene capable of directing subclass development and driving RANKL overexpression during OSA tumorigenesis. Finally, we uncovered evidence for a PRKAR1A-low subset of human OSA with distinct clinical behavior. Thus, tumor subclasses develop in mice and can potentially provide information toward the molecular stratification of human cancers. |
