Histone modifications are one form of epigenetic information that relate closely to gene regulation. Mutations of the Glu76 residue of histone H2B are frequently found in cancer cells. Many mutations in histone variant genes identified in cancer suggest that the mutations influence the shape and function of corresponding histones. The H2B[E76K] mutant allele was found to be associated with cancer and promote tumorigenesis in mammalian tissue culture systems. The preliminary work by collaboration with Dr. Jonathan Licht’s lab has found that expressing H2B[E76K] alone does not show clear oncogenic activity in transgenic fruit flies. Since this mutation is often observed in the context of other oncogenic mutations, making genetic crosses to co-express the human histone 2B mutant with oncogenic RasV12 is proposed, in order to see whether H2B[E76K] promotes context-dependent malignant transformation. By creating genetic crosses of drosophila co-expressing the human histone 2B mutant with oncogenic RasV12 we will discover the extent to which the histone 2B mutation promotes context-dependent malignant transformation.