Environmental and Molecular Mutagenesis (EMM) Editor's Choice - July 2014
The Editor's Choice for July is "Mechanisms of Chromosomal Instability in Melanoma” by William K. Kaufmann, Craig C. Carson, Bernard Omolo, Adam J. Filgo, Maria J. Sambade, Dennis A. Simpson, Janiel M. Shields, Joseph G. Ibrahim, and Nancy E. Thomas.
Melanoma is the most dangerous type of skin cancer and the leading cause of death from skin disease. It is an aggressive cancer that frequently metastasizes and responds poorly to radiation and chemotherapy. Most troubling is the observation that rates of melanoma are increasing each year. Melanoma cells show high levels of chromosome instability manifested as segmental deletions and amplifications; rates of chromosomal instability were nearly 10-times greater in melanoma cells than in primary human melanocytes. This instability could underlie their propensity to metastasize and be resistant to standard cancer therapies. The investigators used a systems biology approach to investigate the characteristics of chromosomal instability in melanoma cell lines. Bioinformatic analysis identified a signature of gene expression that was correlated with chromosomal instability but this signature failed to generate a significant prediction of melanoma progression in a separate dataset. Thus, while chromosomal instability in melanoma cell lines appears to influence gene function, the chromosomal instability gene expression signature cannot identify more aggressive tumors. In contrast, a previously described signature of p53-dependent DNA damage checkpoint function was prognostic of melanoma progression. The chromosome instability gene signature also provided no clues to the mechanisms of instability. While chromosomal instability was associated with many alterations in the DNA damage response pathway, no single element of the DNA damage response elements that were studied was correlated with instability. The results point to a complex and multifactorial mechanism for the development of chromosome instability in melanoma. These studies emphasize that chromosome instability phenotypes have a complex etiology and that this must be considered when developing assays of tumor progression probability and the development of more effective treatments for melanoma. Environ. Mol. Mutagen. 55:457–471, 2014. © 2014 Wiley Periodicals, Inc.