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首页> 外文期刊>Pathology Research International >Genetic and Epigenetic Events Generate Multiple Pathways inColorectal Cancer Progression
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Genetic and Epigenetic Events Generate Multiple Pathways inColorectal Cancer Progression

机译：遗传和表观遗传事件在结直肠癌进展中产生多种途径

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Colorectal cancer (CRC) is one of the most common causes of death, despite decades of research. Initially considered as a disease due to genetic mutations, it is now viewed as a complex malignancy because of the involvement of epigenetic abnormalities. A functional equivalence between genetic and epigenetic mechanisms has been suggested in CRC initiation and progression. A hallmark of CRC is its pathogenetic heterogeneity attained through at least three distinct pathways: a traditional (adenoma-carcinoma sequence), an alternative, and more recently the so-called serrated pathway. While the alternative pathway is more heterogeneous and less characterized, the traditional and serrated pathways appear to be more homogeneous and clearly distinct. One unsolved question in colon cancer biology concerns the cells of origin and from which crypt compartment the different pathways originate. Based on molecular and pathological evidences, we propose that the traditional and serrated pathways originate from different crypt compartments explaining their genetic/epigenetic and clinicopathological differences. In this paper, we will discuss the current knowledge of CRC pathogenesis and, specifically, summarize the role of genetic/epigenetic changes in the origin and progression of the multiple CRC pathways. Elucidation of the link between the molecular and clinico-pathological aspects of CRC would improve our understanding of its etiology and impact both prevention and treatment.
机译：尽管进行了数十年的研究，但结直肠癌（CRC）是最常见的死亡原因之一。最初被认为是由于基因突变引起的疾病，由于涉及表观遗传异常，现在被视为复杂的恶性肿瘤。在CRC的起始和进展中已经提出了遗传机制与表观遗传机制之间的功能对等。 CRC的标志是它的致病性异质性至少可以通过三种不同的途径实现：传统途径（腺瘤-癌序列），替代途径，以及最近所谓的锯齿状途径。尽管替代途径更具异质性且特征较少，但传统途径和锯齿途径似乎更加同质且明显不同。结肠癌生物学中一个尚未解决的问题涉及起源细胞以及不同途径起源于隐窝隔室。基于分子和病理学证据，我们建议传统的和锯齿状的途径起源于不同的隐窝室，解释它们的遗传/表观遗传学和临床病理学差异。在本文中，我们将讨论CRC发病机理的最新知识，尤其是总结遗传/表观遗传变化在多种CRC途径的起源和进展中的作用。阐明CRC的分子和临床病理方面之间的联系将增进我们对CRC病因的了解并影响预防和治疗。

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