Fetal cell carcinogenesis of the thyroid: A modified theory based on recent evidence
Fetal cell carcinogenesis of the thyroid: A modified theory based on recent evidence
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DOI：
10.1507/endocrj.ej13-0517
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发表时间：
2014-04-01
影响因子：
2
通讯作者：
Takano, Toru
中科院分区：
文献类型：
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作者：
Takano, Toru
甲状腺癌细胞被认为是通过多步致癌作用产生的，其中癌细胞来源于甲状腺细胞，通过对它们的基因组的多次损伤，特别是在加速增殖或促进恶性表型的癌基因或抑癌基因中，例如侵入周围组织或转移到远处器官的能力，直到提出一个新的假说，胎儿细胞致癌作用。在胎儿细胞癌变过程中，甲状腺肿瘤细胞被认为是由三种类型的胎儿甲状腺细胞通过增殖而不分化而衍生的，所述三种类型的胎儿甲状腺细胞仅存在于胎儿或幼儿中，即甲状腺干细胞（TSC）、成甲状腺细胞和前甲状腺细胞。基因组改变，如RET/PTC和PAX 8-PPAR γ 1重排和BRAF基因突变，通过阻止甲状腺胎儿细胞分化发挥致癌作用。胎儿细胞癌变有效地解释了最近关于甲状腺癌的分子和临床证据，包括甲状腺癌起始细胞（TCIC），它强调了识别干细胞和阐明癌症研究中器官发育的分子机制的重要性。它介绍了三个重要的概念，反向方法，干细胞危机和成熟和不成熟的癌症。此外，这意味着对癌症组织中的一小部分细胞的分析将是建立未来实验室测试的关键技术。相反，大量分析，如基因表达谱，全基因组扫描，蛋白质组学分析可能有一定的局限性，因为它们只能提供基于许多细胞的信息。
Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPAR gamma 1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.