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      Origin and Progression of Thyroid Epithelial Tumours: Cellular and Molecular Mechanisms

      Hormone Research in Paediatrics

      S. Karger AG

      ras, ret, gsp, Thyroid-stimulating hormone, Thyroid, Oncogene, Tumour-suppressor gene, Differentiation, p53

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          Tumours of the thyroid follicular cell are proving to be one of the most informative models for ‘dissecting’ the molecular genetics of multi-stage human tumorigenesis. Early thyroid tumour development is closely correlated with mutation of five alternative genes, ras, ret, trk, gsp and the TSH receptor, associated with different tumour phenotypes, providing an excellent example of genotype/phenotype correlation. For two of these genes, ras and ret, there is also direct experimental evidence from gene transfer studies that they are sufficient to initiate tumorigenesis, one of very few situations where such proof of causality has been obtained for a human tumour. Much less is known of the molecular basis of malignant transformation in thyroid. However, the rare, further progression to undifferentiated (anaplastic) cancer provides a particularly clear-cut illustration of the role of the tumour-suppressor gene p53 in human cancer. Furthermore, in vitro data suggest the intriguing possibility that the anaplastic phenotype results from a combination of p53 mutation together with a spontaneous switch in differentiation programme, i.e. co-operation between a genetic and an epigenetic event.

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          Author and article information

          Horm Res Paediatr
          Hormone Research in Paediatrics
          S. Karger AG
          09 December 2008
          : 47
          : 4-6
          : 145-157
          Cancer Research Campaign Thyroid Tumour Biology Group, Department of Pathology, University of Wales College of Medicine, Cardiff, UK
          185458 Horm Res 1997;47:145–157
          © 1997 S. Karger AG, Basel

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          Page count
          Pages: 13
          Recent Progress on the Molecular Aspects of Endocrine Tumors: Clinical Implications


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