Fetal cell carcinogenesis of the thyroid: a modified theory based on recent evidence.
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-PPARγ1 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.
Department of Laboratory Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Toru
T
Takano
D053687:Adult Stem Cells / Q000473:pathology*; D000818:Animals; D063646:Carcinogenesis; D049109:Cell Proliferation; D053686:Fetal Stem Cells / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000473:pathology*; D038081:Organogenesis; D013961:Thyroid Gland / Q000196:embryology / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000503:physiopathology