Ennet: exert enhaner-only somatic mutations to discover potential cancer-driving biological networks

Cui, Y.; Niu, Y.; Teng, X.; Wang, D.; Luo, H.; Zhang, P.; Wu, W.; He, S.; Luo, J.; Chen, R.

doi:10.1101/216226

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bioRxiv · 10.1101/216226

Ennet: exert enhaner-only somatic mutations to discover potential cancer-driving biological networks

Cui, Y.·Niu, Y.·Teng, X.·Wang, D.·Luo, H.·Zhang, P.·Wu, W.·He, S.·Luo, J.·Chen, R.

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Abstract

Whole genome sequencing technology has facilitated the discovery of a large number of somatic mutations in enhancers (SMEs), whereas the utility of SMEs in tumorigenesis has not been fully explored. Here we present Ennet, a method to comprehensively investigate SMEs enriched networks (SME-networks) in cancer by integrating SMEs, enhancer-gene interactions and gene-gene interactions. Using Ennet, we performed a pan-cancer analysis in 2004 samples from 8 cancer types and found many well-known cancer drivers were involved in the SME-networks, including ESR1, SMAD3, MYC, EGFR, BCL2 and PAX5. Meanwhile, Ennet also identified many new networks with less characterization but have potentially important roles in cancer, including a large SME-network in medulloblastoma (MB), which contains genes enriched in the glutamate receptor and neural development pathways. Interestingly, SME-networks are specific across cancer types, and the vast majority of the genes identified by Ennet have few mutations in gene bodies. Collectively, our work suggests that using enhancer-only somatic mutations can be an effective way to discover potential cancer-driving networks. Ennet provides a new perspective to explore new mechanisms for tumor progression from SMEs.

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Cui, Y., Niu, Y., Teng, X., Wang, D., Luo, H., Zhang, P., Wu, W., He, S., Luo, J., Chen, R.. 2017-11-08. Ennet: exert enhaner-only somatic mutations to discover potential cancer-driving biological networks. https://doi.org/10.1101/216226

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