Project description:To explore the roles of cell-type specific methylation QTL (meQTL) for melanoma GWAS annotation, we generated DNA methylation data from the same sample set as our previouse eQTL study including 106 primary melanocyte cultures. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs in 106 primary melanocyte cultures. To be able to identify the DNA methylation probes whose methylation levels are correlated with germline genetic variants including the ones associated with melanoma, meQTL analysis was performed in these 106 primary melanocyte cultures using the same method as we did for eQTL study.
Project description:Melanoblastoma-bearing Libechov minipigs (MeLiM) provide an animal model for the study of spontaneous cutaneous melanoma. We compared the serial analysis of gene expression (SAGE) profile between normal skin melanocytes and melanoma cells from a pulmonary metastasis of MeLiM. Keywords: disease state study To minimise the contribution of cells other than melanocytes, we constructed SAGE libraries from a primary culture of melanoma cells derived from a pulmonary melanoma metastasis of a young MeLiM and from a pigmented melanocyte cell line, PigMel, derived from the skin of a healthy Meishan pig.
Project description:Cutaneous malignant melanoma (CMM) lacks targeted therapies beyond the oft-circumvented BRAF inhibitors. Part of the difficulty in treating melanomas has been attributed to a strong survival program controlled by melanocyte transcription factors such as MITF - a phenomenon first described in melanoma as “lineage dependency.” Recently, a highly selective covalent CDK7 inhibitor (THZ1) has been shown to potently suppress the growth of various cancers through the depletion of master transcription-regulating oncogenes and the disruption of their attendant super-enhancers. We now show that melanoma cells are highly sensitive to CDK7 inhibition and that a melanocyte “lineage cluster,” whose members are transcriptionally driven by super-enhancers, is also strongly suppressed by THZ1. These results point to CDK7 inhibition as a viable strategy to deprive oncogenic transcription and suppress tumor growth in melanoma.
