Perduca Vittorio, Omichessan Hanane, Baglietto Laura, Severi Gianluca
Laboratoire de Mathématiques Appliquées - MAP5 (UMR CNRS 8145), Université Paris Descartes.
Centre de Recherche en Epidémiologie et Santé des Populations - CESP (UMR INSERM 1018), Université Paris-Saclay, Université Paris-Sud, UVSQ.
Curr Opin Oncol. 2018 Jan;30(1):61-67. doi: 10.1097/CCO.0000000000000418.
In this article, we describe how recent advances in the study of mutational and epigenetic signatures in tumours provide new opportunities to understand the role of the environment and lifestyle in cancer development.
Cancer-related mutational events have been investigated for decades but only recently the wide availability of genomic sequences and epigenomic data from thousands of cancer genomes has made it possible to identify numerous distinct mutational and epigenetic signatures through the application of advanced mathematical models. Some of these signatures have been linked to endogenous factors such as defective DNA repair or the action of APOBEC cytidine deaminases and to exogenous factors such as tobacco smoke, ultraviolet light, aflatoxins, aristolochic acid and ionizing radiation. More recently, it has been shown that exposure to factors such as tobacco smoke may also leave marks in the DNA methylation profile of both normal and tumour tissue in target organs.
The analysis of mutational and epigenetic signatures is a novel and useful tool to study cancer. Their application to experimental studies and to studies with detailed data on environmental exposures and lifestyle is likely to improve our understanding of how the environment and lifestyle influence cancer development and its evolution.
在本文中，我们描述了肿瘤突变和表观遗传特征研究的最新进展如何为理解环境和生活方式在癌症发生中的作用提供新机会。
与癌症相关的突变事件已被研究数十年，但直到最近，来自数千个癌症基因组的基因组序列和表观基因组数据的广泛可得性，才使得通过应用先进的数学模型识别众多不同的突变和表观遗传特征成为可能。其中一些特征与内源性因素如DNA修复缺陷或载脂蛋白B胞苷脱氨酶的作用有关，也与外源性因素如烟、紫外线、黄曲霉毒素、马兜铃酸和电离辐射有关。最近有研究表明，接触烟等因素也可能在靶器官的正常组织和肿瘤组织的DNA甲基化谱中留下印记。
突变和表观遗传特征分析是研究癌症的一种新颖且有用的工具。将它们应用于实验研究以及具有环境暴露和生活方式详细数据的研究，可能会增进我们对环境和生活方式如何影响癌症发生及其演变的理解。
