amplification and deletion in metastatic melanoma and glioblastoma multiforme may have implications for targeted therapeutics and immunotherapy.

Metastatic melanoma has a five-year survival of ~10%, with a paucity of biomarkers predicting metastasis to specific anatomic sites or targeted therapies for metastases. We analyzed 1015 primary and 358 metastatic melanomas and found metastatic disease is enriched for and amplifications compared to primary disease, and amplifications are associated with lower overall survival. amplifications are associated with a higher rate of metastasis to the brain and liver. Two negative regulators of p53, and , are also altered in metastatic melanoma compared to primary disease. These findings suggest that patients with metastatic melanoma have a dysregulated TP53 pathway compared to primary disease. We propose that patients with metastatic melanoma and wild-type may be more likely to benefit from MDM2, MDM4, USP7, and PPM1D inhibitors. Patients with amplification display deep deletions in , alterations also associated with a higher rate of metastasis to the brain. Patients with a deletion have a higher rate of alterations in , and , alterations previously associated with favorable response to immune-checkpoint inhibitors in melanoma. We propose alteration as a potential biomarker to predict response to immunotherapy in melanoma. We found that GBM displays the highest rate of amplifications (9.63%) and deletions (54.39%) across all cancer types. In 592 GBM samples we found that 8.45% display amplification. We suggest that patients with melanoma or GBM and amplifications in and alterations may benefit from combinations of targeted inhibitors of MDM2/4 and CDK4/6, as well as immunotherapy.