Oncogenic alterations reveal key strategies for precision oncology in melanoma treatment

Abstract

Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid tumors, including melanomas, to identify potential drug targets. However, the association between clinical outcomes and the molecular alterations has not yet been fully clarified. We have analyzed the genetic alterations of 108 malignant melanoma patients using the OncoCare panel, which covers 559 genes. Combining clinical features with genetic analysis, we found that patients carrying both POLD1/ALOX12B or POLD1/PTPRT mutations had a significantly lower survival rate. A model was also established to predict side effects through a combination analysis of clinical data and somatic variants, yielding an area under the receiver operating characteristic curve (AUROC) score of 0.87. In addition, we also found that patients with the POLE mutation had a significantly worse clinical outcome to chemotherapy, while patients with the SOX9 mutation had a significantly worse response to immunotherapy. Overall, these results demonstrate the benefits of applying NGS clinical panels and shed light on future directions of personalized therapeutics for the treatment of melanoma.