Abstract
Aberrations in gene expression are a hallmark of cancer cells. Differential tumor-specific transcript levels of single genes or whole sets of genes may be critical for the neoplastic phenotype and important for therapeutic considerations or useful as biomarkers. As an approach to filter out such relevant expression differences from the plethora of changes noted in global expression profiling studies, we searched for changes of gene expression levels that are conserved. Transcriptomes from massive parallel sequencing of different types of melanoma from medaka were generated and compared to microarray datasets from zebrafish and human melanoma. This revealed molecular conservation at various levels between fish models and human tumors providing a useful strategy for identifying expression signatures strongly associated with disease phenotypes and uncovering new melanoma molecules.
Highlights
Melanoma is one of the most aggressive forms of cancer with still rapidly increasing incidence in the western world [1]
Hyperpigmented skin (HP), a massive overproduction of pigment cells that are different in shape from the normal pigment cells that make up the basic pigmentation of the fish skin, but do not show any signs of three-dimensional growth or invasion, was used for comparison
RNA sequencing has so far not been used in fish models to detect global expression changes that are helpful for better understanding processes of tumor growth and progression
Summary
Gene expression signatures of melanomas have been reported [3,4,5,6,7], only few clues were obtained for molecular subtypes that could be of clinical relevance. A further complication widely discussed to camouflage a clear diagnostic gene expression signature, are individual genetic differences and recurrent changes that reflect epiphenomena of the transformed phenotype and the pathological physiology of the melanoma cells. To pinpoint relevant expression patterns common to all tumor subtypes important information can be obtained from a cross-species comparative approach with melanoma animal models. Changes in gene expression that are conserved over large evolutionary distances have a high probability of reflecting common molecular mechanisms critical for the development of the same disease in different organisms [9,10,11]
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