MDA-MB-435 cells are derived from M14 melanoma cells - a loss for breast cancer, but a boon for melanoma research

Background: The tissue of origin of the cell line MDA- MB- 435 has been a matter of debate since analysis of DNA microarray data led Ross et al. ( 2000, Nat Genet 24( 3): 227 - 235) to suggest they might be of melanocyte origin due to their similarity to melanoma cell lines. We have previously shown that MDA- MB435 cells maintained in multiple laboratories are of common origin to those used by Ross et al. and concluded that MDA- MB- 435 cells are not a representative model for breast cancer. We could not determine, however, whether the melanoma- like properties of the MDA- MB- 435 cell line are the result of misclassification or due to transdifferention to a melanoma- like phenotype. Methods: We used karyotype, comparative genomic hybridization ( CGH), and microsatalite polymorphism analyses, combined with bioinformatics analysis of gene expression and single nucleotide polymorphism ( SNP) data, to test the hypothesis that the MDA- MB435 cell line is derived from the melanoma cell line M14. Results: We show that the MDA- MB- 435 and M14 cell lines are essentially identical with respect to cytogenetic characteristics as well as gene expression patterns and that the minor differences found can be explained by phenotypic and genotypic clonal drift. Conclusions: All currently available stocks of MDAMB435 cells are derived from the M14 melanoma cell line and can no longer be considered a model of breast cancer. These cells are still a valuable system for the study of cancer metastasis and the extensive literature using these cells since 1982 represent a valuable new resource for the melanoma research community.