[Fetal cell carcinogenesis hypothesis and the prospect of future laboratory tests].
A novel hypothesis of carcinogenesis, the "fetal cell carcinogenesis" hypothesis, was established based on molecular evidence of thyroid carcinoma. In this hypothesis, cancer cells are derived directly from the remnants of fetal cells, instead of well-differentiated somatic cells by de-differentiation. For example, thyroid cancer cells are generated from three types of fetal thyroid cell, namely, thyroid stem cells (TSCs), thyroblasts, and prothyrocytes by proliferation without differentiation, which results in producing anaplastic, papillary, and follicular carcinoma, respectively. Genomic alternations, such as RET/PTC and PAX8-PPARgamma1 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 evidence regarding cancer, including cancer stem cells, and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. Further, it introduces two important concepts, the reverse approach and stem cell crisis. Analysis of the molecular behavior of a single cell will be a key technique in establishing future laboratory tests. On the other hand, mass analyses such as gene expression profiling, whole genomic scan, and proteomics analysis have definite limitations since they can only provide information based on many cells. In light of these aspects, we started a project to establish FACS-mQ (mRNA quantification after Fluorescence Activated Cell Sorting). In FACS-mQ, cells are sorted by a specific gene expression pattern, and the gene expression profile in sorted cells can be easily analyzed.
Takano
Toru
T
Department of Laboratory Medicine, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. ttakano@labo.med.osaka-u.ac.jp
D002471:Cell Transformation, Neoplastic; D019411:Clinical Laboratory Techniques; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006801:Humans; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013961:Thyroid Gland / Q000196:embryology / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf