Klinische und molekulare Genetik des Schilddrüsenkarzinoms

Thyroid cancer represents a genetically and clinically heterogeneous group of neoplasias and understanding of its molecular aspects has improved significantly during recent years. In papillary cancer, and particularly in its radiation-induced variants, chromosomal rearrangements of the RET/PTC fusion oncogene have been identified as a key genetic event. PAX8-PPARγ rearrangements are a novel and specific oncogenic mechanism in follicular carcinomas. Anaplastic carcinomas are now believed to arise from differentiated tumors through secondary transformation. In medullary thyroid cancer, occurring in the context of familial MEN2 tumor syndrome in up to 30% of cases, activating point mutations of the RET proto-oncogene are a central mechanism. Using a two-step RET mutation analysis, affected family members may now be identified at a preclinical stage, with the option of surgical cure by prophylactic thyroidectomy.