Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of Czech Republic, Videnska 1083, 14200 Prague 4, Czech Republic.
Mutagenesis. 2012 Mar;27(2):211-8. doi: 10.1093/mutage/ger067.
A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of alterations in the TP53 gene, both somatic mutations and inherited sequence variations, in predisposition to CRC and in the prognosis and response to therapy. The available data from association studies have mostly shown contradictory outcomes. The majority of the studies were based on limited sample sizes and focussed on a limited number of polymorphisms, with main being the rs1042522 (Arg72Pro). Thus far, there is no possible generalisation of the role of TP53 as also a predictor of therapeutic response and prognosis. The effects of TP53, and its abnormalities, on the response of tumours to cytotoxic drugs, radiation and chemoradiation are complex. However, from studies it is emerging that the inherited genetics of TP53 pathway components could be utilised to further define patient populations in their abilities to induce p53 activity in response to either DNA damaging or p53-targeted therapies.
功能正常的 TP53 对于保护机体免受癌症发生至关重要。该基因的体细胞突变是包括结直肠癌（CRC）在内的人类肿瘤中最常见的反复出现的扰动之一。然而，TP53 中广泛存在的体细胞突变的斑驳表型和疾病的复杂性阻止了对肿瘤突变分析的直接解释。除了存在体细胞突变外，基因的多态性特征也可能导致正常 TP53 功能的改变，主要以单核苷酸多态性的形式，预计会影响散发性 CRC 的易感性。在本研究中，我们回顾了 TP53 基因的改变，包括体细胞突变和遗传序列变异，在 CRC 的易感性以及预后和对治疗的反应中的潜在作用。来自关联研究的现有数据大多显示出相互矛盾的结果。大多数研究基于有限的样本量，并集中在少数几个多态性上，主要是 rs1042522（Arg72Pro）。到目前为止，还不可能将 TP53 作为治疗反应和预后的预测因子进行一般化。TP53 及其异常对肿瘤对细胞毒性药物、辐射和放化疗反应的影响是复杂的。然而，从研究中可以看出，TP53 途径成分的遗传遗传学可以用于进一步定义患者群体，以确定其在响应 DNA 损伤或 p53 靶向治疗时诱导 p53 活性的能力。
