| First Author | Shao YW | Year | 2019 |
| Journal | Oncogene | Volume | 38 |
| Issue | 2 | Pages | 291-298 |
| PubMed ID | 30093633 | Mgi Jnum | J:269943 |
| Mgi Id | MGI:6273564 | Doi | 10.1038/s41388-018-0444-4 |
| Citation | Shao YW, et al. (2019) Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma. Oncogene 38(2):291-298 |
| abstractText | Leveraging the conserved cancer genomes across mammals has the potential to transform driver gene discovery in orphan cancers. Here, we combine cross-species genomics with validation across human-dog-mouse systems to uncover a new bone tumor suppressor gene. Comparative genomics of spontaneous human and dog osteosarcomas (OS) expose Disks Large Homolog 2 (DLG2) as a tumor suppressor candidate. DLG2 copy number loss occurs in 42% of human and 56% of canine OS. Functional validation through pertinent human and canine OS DLG2-deficient cell lines identifies a regulatory role of DLG2 in cell division, migration and tumorigenesis. Moreover, osteoblast-specific deletion of Dlg2 in a clinically relevant genetically engineered mouse model leads to acceleration of OS development, establishing DLG2 as a critical determinant of OS. This widely applicable cross-species approach serves as a platform to expedite the search of cancer drivers in rare human malignancies, offering new targets for cancer therapy. |
