The Landscape of Tumor Fusion Neoantigens: A Pan-Cancer Analysis

Zhiting Wei; Chi Zhou; Zhanbing Zhang; Ming Guan; Chao Zhang; Zhongmin Liu; Qi Liu

doi:10.1016/j.isci.2019.10.028

The Landscape of Tumor Fusion Neoantigens: A Pan-Cancer Analysis

iScience. 2019 Nov 22:21:249-260. doi: 10.1016/j.isci.2019.10.028. Epub 2019 Oct 18.

Authors

Zhiting Wei¹, Chi Zhou¹, Zhanbing Zhang¹, Ming Guan², Chao Zhang³, Zhongmin Liu⁴, Qi Liu⁵

Affiliations

¹ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
² Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200433, China.
³ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: zhangchao@tongji.edu.cn.
⁴ Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai 200092, China. Electronic address: liu.zhongmin@tongji.edu.cn.
⁵ Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. Electronic address: qiliu@tongji.edu.cn.

Abstract

Compared with SNV&indel-based neoantigens, fusion-based neoantigens are not well characterized. In the present study, we performed a comprehensive analysis of the landscape of tumor fusion neoantigens in cancer and proposed a score scheme to quantitatively assess their immunogenic potentials. By analyzing three large-scale tumor datasets, we demonstrated that (1) the tumor fusion candidate neoantigen burden is not related to the immunotherapy outcome; (2) fusion neoantigens tend to have notably higher immunogenic potentials than SNV&indel-based candidate neoantigens, making them better candidates for cancer vaccines; (3) fusion candidate neoantigens distribute sparsely between individual patients. Although several recurrent candidate neoantigens exist, they usually have extremely low immunogenic potentials, suggesting that vaccination-based cancer immunotherapy must be personalized; (4) compared with fusion mutations involving tumor passenger genes, fusion mutations involving oncogenic genes have remarkably low immunogenic potentials, indicating that they undergo selection pressure during tumorigenesis.

Keywords: Bioinformatics; Cancer; Genomics.