Reviewer 2's Review

“The paper by Ryu, et al applies expression-profiling technology to characterize a well-described panel of human melanoma cell lines. The authors demonstrate that differences in gene expression among these lines allow them to be segregated into 2 groups "aggressive" and "less aggressive". These classifications also match reasonable well with the clinical origin of these lines as either radial growth phase (early, less aggressive) melanomas or aggressive metastatic melanomas. The authors note that in general, the genes affected fall into 3 categories: cell cycle regulators including genes involved in DNA replication and repair; differentiation genes; and genes involved with resistance to apoptosis. Although the broad conclusions are not particularly surprising with respect to groups of genes differentially expressed, the work is an important contribution to the literature. The observation that some known, relevant genes discovered in earlier single gene approaches were also identified in these experiments suggests that many of the new genes identified here are highly relevant. Also, although only 2 cell lines were wild-type for BRAF, no specific BRAF-associated signature could be identified, an important preliminary finding for the field. Interestingly, they found that cell lines derived from vertical growth phase (advanced primary) melanomas were heterogeneous, segregating with either the early, radial growth phase melanomas or with the metastatic melanomas. As it is currently impossible to predict with any certainty which melanomas will metastasize, these early findings may be valuable clues in the search for more accurate clinical predictions. Their finding that NFkB may be a master regulator of invasion and metastases is certainly worth following up.”

N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.