Rearrangements of RET and NTRK1 Tyrosine Kinase Receptors in Papillary Thyroid Carcinomas

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Abstract
A combined cytogenetic and molecular analysis of thyroid tumours has indicated that these neoplasms might represent a significant model for analysing human epithelial cell multi-step cancerogenesis. Thyroid tumours comprise a broad spectrum of lesions with different phenotypes and variable biological and clinical behaviour. Molecular analysis has detected specific genetic alterations in these different tumour types. In particular, the well-differentiated carcinomas of the papillary type are characterised by the activation of the tyrosine kinase receptors (TKRs) RET and NTRK1 proto-oncogenes. Cytogenetic analysis of these tumours has contributed to defining the chromosomal mechanisms leading to the TKRs’ oncogenic activation. The results have shown that, in the majority of the cases, intra-chromosomal inversions of chromosome 10 and of chromosome 1 lead to the formation of RET-derived and NTRK1-derived oncogenes, respectively. Exposure to ionizing radiation is associated with papillary carcinomas, and RET activation has been suggested to be related to this event. All these findings are contributing to the definition of genetic and environmental factors relevant to the pathogenesis of thyroid tumours. Moreover, the molecular characterisation of specific genetic lesions could provide significant information about the association between ionising radiation and RET oncogene activation.