Molecular and genetic diversity in the metastatic process of melanoma

摘要: Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine tumours, we performed gene-expression profiling of 63 obtained from 28 (two or three tumours/patient), followed by analysis their mutational landscape, using targeted deep sequencing 1697 cancer genes DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes tumour lesions within a patient 50% cases. In 18 22 (where matched normal tissue was available), found that multiple were genetically divergent, with one more harbouring 'private' somatic mutations. case, distant subcutaneous metastasis occurring 3 months after an earlier regional lymph node had acquired 37 new coding sequence mutations, including mutations PTEN CDH1. However, BRAF NRAS when present first metastasis, always preserved subsequent metastases. The patterns nucleotide substitutions this study indicate influence UV radiation but possibly also alkylating agents. Our results clearly demonstrate molecularly highly heterogeneous disease continues to progress throughout its clinical course. private aberrations observed on background shared provide evidence continued evolution following divergence common parental clone, might have implications for personalized medicine strategies treatment. Published John Wiley & Sons, Ltd. www.pathsoc.org.uk