NEB mutation is associated with high mutational burden and worse colorectal-cancer survival

Abstract

Background: Nebulin (NEB) as a protein-coding gene have been well demonstrated its vital roles in skeletal muscles but no study for association between NEB mutation and cancer.Methods: Here, we systematically analyzed mutation spectrum of colorectal cancer (CRC) samples and associations between NEB somatic mutation and CRC patients' tumor mutation burden (TMB) and prognosis by using TCGA-COAD project mutation dataset.Results: Mutational signatures detected from CRC samples indicated pivotal roles of defective DNA damage repair process and polymerase activity in CRC initiation. NEB somatic mutation was found in about 16% CRC patients. Besides, NEB mutation was identified as an independent factor for high CRC TMB and inferior prognosis. Significantly mutated gene (SMG) analysis identified several genes including RNF43, SETD1B, MBD6 and so on, whose mutation states were profoundly influenced by NEB mutation and might be tumor driver genes in CRC initiation and progression.Conclusions: In conclusion, NEB might be a novel CRC-related genes that could affect patients' prognosis by perturbing genome instability.