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Better understanding of intrinsic tumor biology has permitted the development of clinical molecular tests that are objective prognostic tools for various cancers, including cutaneous melanoma (CM). A previously validated 31-gene expression profile (31-GEP) test utilizes RT-PCR of primary CM tumors to predict a patient’s risk of recurrence, including sentinel lymph node, locoregional, and distant metastasis events, within 5 years. To develop the test, candidate genes identified in published melanoma gene expression datasets were evaluated for consistency across multiple studies. Herein, we review the methods and data utilized during the development of the 31-GEP test and the known functions of its 28 prognostic genes. Using pathway and protein-protein interaction databases along with literature searches, we demonstrate that the genes assessed by the test are functional components of key melanomaand cancer-relevant biological processes known to contribute to progression and metastasis and are supported by other studies. The genes utilized to assess melanoma risk play significant roles in processes such as cell-cell communication, differentiation, growth regulation, and immune signaling. These findings suggest that many biological processes, rather than a few pathways, contribute to melanoma progression. Thus, capturing these diverse biological events is necessary for accurate prognostication. In conclusion, the 31-GEP test determines risk by assessing key biological processes associated with progression. Evaluating melanoma tumor biology at a molecular level, in addition to histopathological features, identifies high-risk patients who otherwise would be deemed at low risk for recurrence and metastasis by traditional staging methods alone. Furthermore, these genes could be candidates for novel therapeutic interventions.

skin

Genes and biological functions governing intrinsic tumor biology utilized in cutaneous melanoma risk assessment through a clinically available 31-gene expression profile test