Australasian Microarray & Associated Technologies Association, AMATA

Jeffs, A, Glover, M, He, S, Baguley, B* and Eccles, M
Department of Pathology, Dunedin School of Medicine, University of Otago, New Zealand; *Auckland Cancer Society Research Centre, University of Auckland, New Zealand.

Melanoma skin cancer can rapidly progress from a slow-growing surgically curable lesion to aggressive metastatic disease, with high mortality and poor response to current therapies. The mechanisms underlying melanoma progression and resistance to therapeutic agents are not well understood. There are few treatment options once metastasized, and new biomarkers that aid diagnosis, predict clinical outcome, and suggest new therapies are required. We are investigating the molecular basis of melanoma by defining genomic signatures that correlate with invasiveness and tumour phenotype in a panel of metastatic melanoma cell lines. Microarray analysis of 27 cell lines revealed a putative invasive/proliferative gene signature featuring differential expression of the microphthalmia-associated transcription factor (MITF) and related transcriptional networks. We suspected that decreased expression of MITF-mediated melanocyte lineage specification genes might reflect a de-differentiated cell type with increased invasive and metastatic potential. Migration assays confirmed that the gene signature correlated with the invasiveness of the cell lines, and external validation using publicly available data indicated that tumours with the invasive gene signature may be more aggressive. Decreased MITF expression defined a melanoma subtype within a group of patients with significantly shorter survival time, suggesting this signature may be of prognostic benefit to patients with metastatic disease.