Underpining the effects of defective miRNA biogenesis in the formation of thyroid tumors

ABOUT THE PROJECT

Germline pathogenic variants in DICER1 predispose to the development of multiple tumors during childhood. The most prevalent phenotype is multinodular goiter (MNG) that can be associated to highly lethal rare cancers like pleuropulmonary blastoma, pineoblastoma, pituitary blastoma and anaplastic sarcoma of the kidney. DGCR8, another member of the miRNA processing machinery, has been pinpointed as a susceptibility gene for MNG. DICER1 and DGCR8 mutations are also present in thyroid cancers including in aggressive poorly differentiated thyroid cancers (PDTC). Childhood PDTCs are rare and present with a high prevalence of DICER1 mutations. This project seeks to understand the deregulated mechanisms underlying thyroid nodules, MNG and thyroid cancers in patients with a genetic alteration in the miRNA biogenesis pathway and the biological scenarios by which two cell clones sharing the same alteration remain benign or become highly aggressive.