Next Generation Sequencing of mouse melanoma tumors generated with a repressible BRAF construct

Purpose: The goals of this study are to compare NGS-derived transciptomes from engineered mouse tumors with activated BRAF (primary), repressed BRAF (simulating drug treatment- dormant) and tumors which escape dormant state (recurrent) Results: We found conserved expression changes in histone methyltransferase genes (HMT), including Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2), Suppressor Of Variegation 3-9 Homolog 1(SUV39H1), Suppressor Of Variegation 3-9 Homolog 2 (SUV39H2), ASH2 Like, Histone Lysine Methyltransferase Complex Subunit (ASH2L), SET And MYND Domain Containing 2 (SYMD2), and Protein arginine methyltransferase 5 (PRMT5) and histone deacetylases (HDACs) HDACS 7, 9,10, and 11. Overall design: Genetically Engineered mouse was designed to grow BRAFV600E dependent primary melanomas. BRAFV600 construct was designed so that it could be turned off resulting in tumor dormancy. After a period of time the tumors escaped the dormant state and began to grow again generating recurrent tumors.