Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma

摘要: Systematic analyses of cancer genomes promise to unveil patterns genetic alterations linked the genesis and spread human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed genome-wide identification both loss-of-heterozygosity events copy-number in cancer. Here, by integrating SNP array-based maps with gene expression signatures derived from NCI60 cell lines, we identified melanocyte master regulator MITF (microphthalmia-associated transcription factor) as target a novel melanoma amplification. We found that amplification was more prevalent metastatic disease correlated decreased overall patient survival. BRAF mutation p16 inactivation accompanied lines. Ectopic conjunction BRAF(V600E) mutant transformed primary melanocytes, thus can function oncogene. Reduction activity sensitizes cells chemotherapeutic agents. Targeting combination or cyclin-dependent kinase inhibitors may offer rational therapeutic avenue into melanoma, highly chemotherapy-resistant neoplasm. Together, these data suggest represents distinct class 'lineage survival' addiction' oncogenes required for tissue-specific development tumour progression.