Szymańska Katarzyna, Hainaut Pierre
Unit of Molecular Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
Acta Biochim Pol. 2003;50(1):231-8.
TP53 is the most frequently mutated gene in human cancer, with a predominance of missense mutations scattered over 200 codons. In many cancers, specific mutation patterns can be identified, which are shaped by site-specific mutagenesis and by biological selection. In tobacco-related cancers (lung, head and neck), organ-specific patterns are observed, with many mutations compatible with the ones experimentally induced by tobacco carcinogens. In several other cancers, such as squamous cell carcinoma of the oesophagus or hepatocellular carcinoma (HCC), mutation patterns show geographic variations between regions of high and low incidence, suggesting a role for region-specific risk factors. HCC from high-incidence regions showing also a high prevalence of a specific Ser-249 TP53 mutation is one of the most striking examples of a mutagen fingerprint. All such assessments are useful to generate clues on the mutagenic mechanisms involved in human cancer. Moreover, it has been shown that DNA retrieved from plasma can be successfully used for detection of TP53 mutations, which gives hope for earlier more accurate detection of human cancers.
TP53是人类癌症中最常发生突变的基因，错义突变主要散布在200个密码子上。在许多癌症中，可以识别出特定的突变模式，这些模式是由位点特异性诱变和生物选择形成的。在与烟草相关的癌症（肺癌、头颈癌）中，观察到器官特异性模式，许多突变与烟草致癌物实验诱导的突变一致。在其他几种癌症中，如食管鳞状细胞癌或肝细胞癌（HCC），突变模式在高发病率和低发病率地区之间存在地理差异，这表明区域特异性风险因素发挥了作用。来自高发病率地区的HCC也显示出特定的Ser-249 TP53突变的高患病率，这是诱变指纹最显著的例子之一。所有这些评估都有助于生成有关人类癌症诱变机制的线索。此外，已经表明从血浆中提取的DNA可以成功用于检测TP53突变，这为更早、更准确地检测人类癌症带来了希望。
