Gene expression profiling of primary cutaneous melanoma: Expression of replication origins firing genes predicts clinical outcome

8024 Background: Gene-expression profiling in human cutaneous melanomas is impaired by the difficulty in getting access to a retrospective collection of frozen tumors. Thus, compared to other tumors, gene expression profiling data on human cutaneous melanomas are scarce, and data with prognostic implication are entirely lacking. In order to better understand the progression of this tumor and to identify key genes involved in melanoma prognosis, we correlated gene-expression profiles with clinical outcome in a cohort of 83 patients with primary melanoma. Methods: A class comparison and class prediction analysis was performed to identify genes able to predict 4-years. distant metastasis free-survival in 58 primary melanomas with at least 4-years follow-up or intercurrent distant metastasis or death. Results were also validated at the protein level in an independent population of 176 primary melanomas with a median clinical follow-up of 8.5 years. Results: We identified a set of sequences discriminating between primary melanomas associated with good and poor prognosis. Some of these sequences correspond to key-genes in the regulation of replication origins firing, such as mini-chromosome maintenance genes and geminin. The prognostic value of overexpression of replication origins firing genes is independent from thickness, ulceration, age and sex. Conclusions: This study has identified key-genes associated with in vivo metastatic dissemination of cutaneous melanomas. Some of our data provide new diagnostic tools for the accurate diagnosis of melanoma and shed new light on the molecular mechanisms underlying poor prognosis in melanoma patients. As some of these molecules are currently under study as targets for therapy, our data can have significant impact on the development of new melanoma therapies. No significant financial relationships to disclose.