Xue Xuemin, Dong Lin, Burke Edwina, Xue Liyan, Lu Yong-Jie
Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.
Centre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London London EC1M 6BQ, UK.
Am J Cancer Res. 2022 Apr 15;12(4):1866-1883. eCollection 2022.
suppresses tumorigenesis through multiple cellular functions/mechanisms, including genomic stability surveillance. Recently, it has also be reported for its role in cancer immune response modulation. Deficiency in DNA repair pathways lead to the accumulation of genomic alterations and tumor mutation burden and in consequence resulting in the activation of immune response. We investigated the interaction of and DNA repair gene mutations and their impact on tumor mutation burden and immune response in human malignancies by mining cBioPortal data of a range of human cancers. We found that in the majority of human cancers, mutations are equally distributed between DNA repair gene mutation positive and negative cases and in a number of human cancers, and DNA repair gene mutations have a tendency of co-occurrence. Only in colorectal cancer, there is a tendency of 'mutual exclusivity' of mutations in and DNA repair genes. In most tumors, and DNA repair gene mutations have synergistic/additive effect in increasing tumor mutation burden, but not in colorectal cancer where they are mutually exclusive. The impact of and DNA repair gene mutations and their interaction on tumor microenvironment immune cells are complex and tumor type specific and not always correlated with tumor mutation burden. In colorectal cancers, these two types of mutations resulted in similar immune cell subpopulation changes and in tumors where the mutations have a tendency of co-occurrence, showed dominant roles on immune response, although they can also counter-act each other for their effect on certain immune cell subtypes.
通过多种细胞功能/机制抑制肿瘤发生，包括基因组稳定性监测。最近，也有报道称其在癌症免疫反应调节中发挥作用。DNA修复途径的缺陷导致基因组改变和肿瘤突变负担的积累，进而导致免疫反应的激活。我们通过挖掘一系列人类癌症的cBioPortal数据，研究了[具体基因名称未给出]与DNA修复基因突变的相互作用及其对人类恶性肿瘤中肿瘤突变负担和免疫反应的影响。我们发现，在大多数人类癌症中，[具体基因名称未给出]突变在DNA修复基因突变阳性和阴性病例中分布均匀，并且在一些人类癌症中，[具体基因名称未给出]与DNA修复基因突变有共现的趋势。仅在结直肠癌中，[具体基因名称未给出]与DNA修复基因的突变存在“相互排斥”的趋势。在大多数肿瘤中，[具体基因名称未给出]与DNA修复基因突变在增加肿瘤突变负担方面具有协同/累加效应，但在结直肠癌中它们是相互排斥的。[具体基因名称未给出]与DNA修复基因突变及其相互作用对肿瘤微环境免疫细胞的影响是复杂的且具有肿瘤类型特异性，并并不总是与肿瘤突变负担相关。在结直肠癌中，这两种类型的突变导致相似的免疫细胞亚群变化，并且在突变有共现趋势的肿瘤中，[具体基因名称未给出]在免疫反应中起主导作用，尽管它们在对某些免疫细胞亚型的作用上也可能相互抵消。
