Department of Medical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Cancer Med. 2021 Jan;10(1):135-142. doi: 10.1002/cam4.3579. Epub 2020 Oct 30.
POLE mutations, which lead to an ultramutated phenotype in colorectal cancer (CRC), have been reported as a promising marker in immunotherapy. We performed sequencing of CRC cases in Zhejiang University (ZJU) and extracted obtainable data from recently published results, including The Cancer Genome Atlas (TCGA), Japanese studies and clinical trials, to present clinical patterns of POLE driver-mutated CRC and reveal its heterogeneity. The rate of somatic POLE driver mutations has been reported as 2.60% (ZJU cohort), 1.50% (TCGA cohort), 1.00% (Japan cohort), and 1.00% (Lancet cohort). POLE driver mutations show a clearly increased mutation burden (mean TMB: 217.98 mut/Mb in ZJU; 203.13 mut/Mb in TCGA). Based on pooled data, more than 70.00% of patients with POLE driver mutations were diagnosed before they were 55 years old and at an early disease stage (Stage 0-II >70.00%), and more than 70.00% were male. Among Asian patients, 68.40% developed POLE driver mutations in the left-side colon, whereas 64.00% of non-Asian patients developed them in the right-side colon (p < 0.01). The top three amino acid changes due to POLE driver mutations are P286R, V411L, and S459F. Investigators and physicians should ascertain the heterogeneity and clinical patterns of POLE driver mutations to be better equipped to design clinical trials and analyze the data.
POLE 突变导致结直肠癌（CRC）的超高突变表型，已被报道为免疫治疗中的一个有前途的标志物。我们对浙江大学（ZJU）的 CRC 病例进行了测序，并从最近发表的结果中提取了可获得的数据，包括癌症基因组图谱（TCGA）、日本研究和临床试验，以展示 POLE 驱动突变型 CRC 的临床模式，并揭示其异质性。体细胞 POLE 驱动突变的发生率报告为 2.60%（ZJU 队列）、1.50%（TCGA 队列）、1.00%（日本队列）和 1.00%（柳叶刀队列）。POLE 驱动突变显示出明显增加的突变负担（ZJU 中的平均 TMB：217.98 mut/Mb；TCGA 中的 203.13 mut/Mb）。基于汇总数据，超过 70.00%的 POLE 驱动突变患者在 55 岁之前被诊断出疾病处于早期阶段（0 期-II 期>70.00%），且超过 70.00%为男性。在亚洲患者中，68.40%的患者在左侧结肠发生 POLE 驱动突变，而 64.00%的非亚洲患者在右侧结肠发生 POLE 驱动突变（p<0.01）。由于 POLE 驱动突变而导致的前三种氨基酸变化是 P286R、V411L 和 S459F。研究人员和医生应该确定 POLE 驱动突变的异质性和临床模式，以便更好地设计临床试验和分析数据。
