Investigating the utility of human melanoma cell lines as tumour models

Melanoma researchers utilize cell lines to model many tumour phenomena. It is thus important to understand similarities and differences between cell lines and the tumours that they represent, so that the optimal models can be chosen to answer specific research questions. Herein, we compared the transcriptomes of 42 melanoma cell lines to hundreds of tumours from The Cancer Genome Atlas and thousands of single melanoma cells. Tumour purity was accounted for using the ESTIMATE algorithm, so that differences likely resulting from non-tumour cells could be accounted for. In addition, UV mutational signatures and the expression of skin-associated genes were analyzed in order to identify the putative origin of various cell lines. We found the transcriptional and mutational characteristics of melanoma cell lines to mirror those of the tumours, with the exception of immune-associated transcripts, which were absent in cell culture. We also determined cell lines that highly or poorly recapitulate melanomas and have identified colon (COLO 741) and lung (COLO 699) cancer cell lines that may actually be melanoma. In summary, this study represents a comprehensive comparison of melanoma cell lines and tumours that can be used as a guide for researchers when selecting melanoma cell line models.