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. 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.