Voutsadakis Ioannis A
Division of Medical Oncology, Department of Internal Medicine, Sault Area Hospital, Sault Ste Marie, Ontario, Canada; Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, Canada.
Gene. 2018 Mar 20;647:31-38. doi: 10.1016/j.gene.2018.01.030. Epub 2018 Jan 7.
Mutations in the exonuclease domain of polymerase epsilon (POLE), an enzyme of DNA synthesis, are involved in a newly described syndrome of colorectal polyposis and cancer, and have been associated with a high mutation burden with or without microsatellite instability (MSI) phenotype. The exonuclease domain of POLE executes a proofreading function that decreases the mutation rate during DNA replication by an estimated of one to two orders. The high mutation burden resulting from its loss of function could create a load of neo-antigens that would put the neoplastic cells in severe disadvantage of an immune attack if properly presented to the immune system. This paper investigates the mutagenic effect of different POLE mutations in various cancers, in published genomic studies and the effect that these POLE mutations have in selecting for mutations of the β2 microglobulin (B2M) gene involved in antigen presentation.
聚合酶ε（POLE）是一种参与DNA合成的酶，其核酸外切酶结构域中的突变与一种新描述的结直肠息肉病和癌症综合征有关，并且无论有无微卫星不稳定性（MSI）表型，都与高突变负担相关。POLE的核酸外切酶结构域执行校对功能，可使DNA复制过程中的突变率降低大约一到两个数量级。其功能丧失导致的高突变负担可能会产生大量新抗原，如果这些新抗原被恰当地呈递给免疫系统，将会使肿瘤细胞在免疫攻击中处于极为不利的地位。本文在已发表的基因组研究中，调查了不同POLE突变在各种癌症中的诱变作用，以及这些POLE突变在选择参与抗原呈递的β2微球蛋白（B2M）基因突变方面所产生的影响。
