Blanchard Jean-Marie
Institut de Génétique Moléculaire, Cnrs UMR 5535, IFR24, Equipe labellisée La Ligue, 1919, route de Mende, 34293 Montpellier, France.
Med Sci (Paris). 2003 Feb;19(2):187-99. doi: 10.1051/medsci/2003192187.
Our vision of the cancer cell has dramatically changed since the discovery of proto-oncogenes, whose deregulation was proposed to mimic normal growth signalling. This notion, linking cancer to cell signalling pathways, has progressively led the way to the concept of the mutator phenotype, in which genetic instability plays an essential role in the onset of cancer. This then transformed cancer into a DNA repair disease. However, as foreseen decades ago by cytogeneticists, point mutations are not sufficient to give a full picture of the whole process. As a result, aneuploidy, rather than gene mutation, has been proposed as the explanation for the complex changes observed in cancer cells. The culprits were found among genes involved in the control of the cell division cycle, and work aimed at understanding the regulation of S phase and mitosis have yielded new insights into our understanding of cancer.
自从原癌基因被发现以来,我们对癌细胞的认识发生了巨大变化。原癌基因的失调被认为会模拟正常的生长信号。这种将癌症与细胞信号通路联系起来的观点,逐渐引出了突变体表型的概念,其中基因不稳定在癌症的发生中起着至关重要的作用。这进而将癌症转变为一种DNA修复疾病。然而,正如细胞遗传学家几十年前所预见的那样,点突变不足以全面描述整个过程。因此,有人提出非整倍体而非基因突变才是癌细胞中观察到的复杂变化的解释。罪魁祸首存在于参与细胞分裂周期控制的基因中,旨在理解S期和有丝分裂调控的研究为我们对癌症的理解带来了新的见解。