POLE
小结
POLE是抑癌基因，编码蛋白是DNA聚合酶ε的催化亚基，是一种参与DNA复制和修复的酶。POLE含有外切核酸酶“校对”结构域。POLE的胚系功能缺失突变与息肉病和结直肠癌的发生相关。在结肠癌，直肠癌和子宫内膜癌中，POLE外切核酸酶结构域中的几个热点突变被鉴定为影响其校对能力并导致超高突变率。在子宫内膜癌和结肠直肠癌也检测到了POLE的体细胞突变。
POLE encodes the catalytic subunit of DNA polymerase epsilon, an enzyme involved in DNA replication and repair. Select POLE mutations lead to ultra-high mutation rates, most frequently in endometrial and colorectal cancer. POLE is the catalytic subunit of DNA polymerase ε, the replicative DNA polymerase that extends the leading strand during DNA replication. POLE contains an exonuclease "proofreading" domain, which replaces incorrectly incorporated nucleotides spontaneously during faithful replication. Germline loss-of-function mutations in POLE have been identified in patients with polyposis and predisposition to colorectal cancer. Several recurrent mutation hotspots in the exonuclease domain of POLE have been identified as impacting its proofreading capability and leading to ultra-high mutation rates, primarily in cancers of the colon, rectum and endometrium. Somatic mutations in the proofreading domain of POLE have been reported in endometrial cancers and colorectal cancers. In some contexts, POLE mutations have been associated with hypermutation, increased mutation load and better response to checkpoint inhibition in human cancers. Patients with mutated, proofreading-deficient POLE in endometrial cancer have been shown to have better outcomes.