Abstract 4505: Pan-cancer analysis of fusion gene druggability and neoantigen potential

Fusion genes are a well known type of oncogenic mutation, in which a genomic rearrangement, such as e.g. a translocation, inversion or deletion, joins together parts of two genes, which normally are not located adjacent to each other. In the context of cancer driver mutations, the result of this rearrangement is a novel chimeric gene with oncogenic potential. While fusion genes have been known longest in hematological malignancies, over the last years they have been shown to occur in nearly all types of cancers studied. Notable examples include ETS-family fusions, such as TMPRSS2-ERG, in prostate cancer. In previous work, we have used our FusionSCOUT fusion gene detection pipeline to analyze over 8000 cancer samples from 28 different TCGA cancer types. In this study, we extend this target discovery to further characterize the genomic alteration contexts in which gene fusions occur, both by examining the copy number states at inferred rearrangement breakpoints, as well as by correlating the numbers of fusion genes identified in tumors with the level of genomic instability in the tumors. We also analyze the frequency at which different druggable protein domains occur in fusion genes, comparing these to the expected random distribution. Finally, we predict, for each tumor, the neoantigen potential of the identified fusion proteins and compare this to the same predictions for simple somatic mutations, in order to characterize the contribution of fusion proteins to neoantigen load. In summary, we extend our pan-cancer fusion gene identification analysis with a detailed characterization of the genomic alteration contexts at which fusion genes occur. We also report on the drug treatment potential of fusion genes, both in terms of small molecule drugs, as well as highlight the degree to which fusion gene derived chimeric proteins should be taken into account when estimating the neoantigen load of tumors. Citation Format: Henrik Edgren, Anja Ruusulehto, Kalle Ojala, Maria Laaksonen. Pan-cancer analysis of fusion gene druggability and neoantigen potential. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4505.