Applications of Genomics in Melanoma Oncogene Discovery

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Melanoma oncogenes

Genetic mutations involving numerous genes have been linked to melanoma genesis and progression. These genes encompass many signaling pathways, including the receptor tyrosine kinase (RTK), phosphatidylinositol-3-kinase (PI(3)K), retinoblastoma (RB), p53, Wnt, and NF-kB pathways. The supporting evidence implicating these oncogenes in melanoma ranges from positional cloning studies in familial melanoma to elevated frequencies of mutation or amplification in patient cohorts, to functional studies

Melanoma oncogenes and personalized medicine

The completion of the human genome project marked the beginning of the genomic era in biology. However, for this knowledge to truly transform medicine, accessible and affordable technologies are needed that can probe the genomes of many individuals to understand the genetic basis of disease and, ultimately, to stratify cancer patients in the clinical arena for optimal therapy. For cancer in particular, the ability to profile the genetic makeup of a patient's tumor can indicate which pathways

Summary

The identification of melanoma oncogenes, such as NRAS, BRAF, MITF, NEDD9, and KIT, have led to an improved understanding of the biology of melanoma. These discoveries have come about from a variety of genomic approaches, including systematic DNA sequencing, chromosomal copy number profiling, gene expression profiling, evolutionary conservation analysis, and RNA interference. Despite these initial successes, the genetic basis of melanoma progression remains largely uncharacterized. It is clear

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    This work was supported by Grant No. DP2OD002750 (NIH), the Burroughs-Wellcome Fund, and the Starr Cancer Consortium.

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