Genetické příčiny vzniku karcinomů štítné žlázy

Genetic Causes ofthe Thyroid Carcinomas

Thyroid carcinomas represent only 1 % of all human malignancies, but more than 90 % of endocrine tumors. It canbe histologically divided into papillary, follicular, anaplastic oř medullary thyroid carcinomas. Here we report thegenetic causes of the development of these tumors. For papillary thyroid carcinoma formation of fused genes oftyrosine kinases (RET proto-oncogene, NTRK1 proto-oncogene and met proto-oncogene) with other genes is typical.They can activate these kinases and induce mutation in BRAF gene. The presence of PAX8/PPARy fused gene andras mutations are important in the development of follicular thyroid carcinoma. Anaplastic thyroid carcinoma deri vesfrom the dedifferentiation of papillary and follicular carcinomas as a consequence of mutation oř loss of heterozygozity in p53 gene. Medullary thyroid carcinoma comes from parafollicular C-cells, where point somatic andgerm-line mutations (in familial form of medullary thyroid carcinoma oř in multiple endocrine neoplasia type 2) inthe RET proto-oncogene determine its development. Identification of these specific genetic alternations for eachtype of carcinoma can contribute to precision ofthe diagnosis, explanation ofthe origin of carcinomas, establishmentof prognosis of the disease oř in future as a tool for the target gene therapy

Key words:
carcinoma, thyroid, genetics, oncogene, fused gene, mutation, tumor suppressor gene