Ilyas M, Tomlinson I P
Colorectal Cancer Unit, Imperial Cancer Research Fund, St Mark's Hospital, Harrow, UK.
Histopathology. 1996 May;28(5):389-99. doi: 10.1046/j.1365-2559.1996.339381.x.
The model of colorectal tumorigenesis put forward by Fearon and Vogelstein has had great influence on molecular oncology. They proposed that a series of mutations occur in the progression from normal cells to colorectal cancer and that these mutations are associated with the histological features of such tumours. Several postulates of the model appear to be correct, particularly its emphasis on the stepwise accumulation of genetic changes and the inclusion of mutations at the adenomatous polyposis coli (APC) and TP53 loci. Since the publication of the original model, however, mutations at other loci have been identified which may be alternatives or additions. There is also evidence to suggest that some colorectal cancers develop along a different genetic pathway. In this review, we discuss how tumour development can occur as Darwinian evolution through selection of advantageous somatic mutations. The non-random nature of mutation selection gives rise to genetic pathways of tumorigenesis. In addition, we consider the Fearon and Vogelstein model, its shortcomings and possible additions to it. The evidence suggests that not all colorectal cancers follow the same genetic pathway during carcinogenesis.
费伦和沃格尔斯坦提出的结直肠癌发生模型对分子肿瘤学产生了重大影响。他们提出，从正常细胞发展到结直肠癌的过程中会发生一系列突变，且这些突变与此类肿瘤的组织学特征相关。该模型的几个假设似乎是正确的，尤其是其对基因变化逐步积累的强调，以及对腺瘤性息肉病（APC）和TP53基因座突变的纳入。然而，自原始模型发表以来，已发现其他基因座的突变，这些突变可能是替代或补充。也有证据表明，一些结直肠癌沿着不同的遗传途径发展。在本综述中，我们讨论肿瘤如何通过选择有利的体细胞突变以达尔文进化的方式发生发展。突变选择的非随机性质产生了肿瘤发生的遗传途径。此外，我们考虑了费伦和沃格尔斯坦模型、其缺点以及可能的补充内容。证据表明，并非所有结直肠癌在致癌过程中都遵循相同的遗传途径。
