Department of Pathology, Institut Universitaire du Cancer-Oncopole de Toulouse; Centre Hospitalier Universitaire (CHU), Toulouse, France
Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III Paul Sabatier, INSERM, CRCT, Toulouse, France.
Life Sci Alliance. 2023 Oct 27;7(1). doi: 10.26508/lsa.202302290. Print 2024 Jan.
Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the alterations influence similar strength tumorigenesis, immune microenvironment, and treatment response. In this review, we summarize the current understanding of the mechanisms and consequences of mutations in human malignancies; we highlight the heterogeneity of mutation rate and cancer aggressiveness among POLE variants, propose some mechanistic basis underlining such heterogeneity, and discuss novel considerations for the choice and efficacy of therapies of POLE tumors.
种系致病性变体在复制 DNA 聚合酶 Pol ε 的外切酶结构域中，该酶由 基因编码，通过诱导超突变表型，主要导致结直肠和子宫内膜肿瘤。目前尚不清楚所有的 改变是否以相似的强度影响肿瘤发生、免疫微环境和治疗反应。在这篇综述中，我们总结了目前对人类恶性肿瘤中 突变机制和后果的认识；我们强调了 POLE 变异中突变率和癌症侵袭性的异质性，提出了一些潜在的机制基础，并讨论了 POLE 肿瘤治疗选择和疗效的新考虑因素。
