Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study
Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study
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DOI：
10.1016/s2468-1253(16)30014-0
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发表时间：
2016-11-01
影响因子：
35.7
通讯作者：
Church, David N.
中科院分区：
文献类型：
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作者：
Domingo, Enric;Freeman-Mills, Luke;Church, David N.
精确的癌症医学依赖于使用可能以非常适度的频率发生的生物标志物来定义不同的肿瘤亚组。一个这样的亚组包括异常突变的患者，方法我们从临床试验中研究了POLE校正结构域突变与结直肠癌临床病理变量和免疫应答的关系，（维克托、QUASAR 2和PETACC-3）和结肠直肠癌组群（莱顿大学医学中心1和2、奥斯陆1和2、伯尔尼、AMC-AJCC-II和Epicolon-1）。我们随后通过考克斯回归分析这些研究中4500多例患者的个体数据，研究了其与II/III期结直肠癌预后的关系。（1.0%）的6517结直肠癌，在6277例同时测定两种标志物的病例中，与错配修复缺陷（MMR-D）相互排斥（66例无，833例[13.4%]）6211; p
Background Precision cancer medicine depends on defining distinct tumour subgroups using biomarkers that may occur at very modest frequencies. One such subgroup comprises patients with exceptionally mutated (ultramutated) cancers caused by mutations that impair DNA polymerase epsilon (POLE) proofreading.Methods We examined the association of POLE proofreading domain mutation with clinicopathological variables and immune response in colorectal cancers from clinical trials (VICTOR, QUASAR2, and PETACC-3) and colorectal cancer cohorts (Leiden University Medical Centre 1 and 2, Oslo 1 and 2, Bern, AMC-AJCC-II, and Epicolon-1). We subsequently investigated its association with prognosis in stage II/III colorectal cancer by Cox regression of pooled individual patient data from more than 4500 cases from these studies.Findings Pathogenic somatic POLE mutations were detected in 66 (1.0%) of 6517 colorectal cancers, and were mutually exclusive with mismatch repair deficiency (MMR-D) in the 6277 cases for whom both markers were determined (none of 66 vs 833 [13.4%] of 6211; p