Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells
Giulia Calafato, Floriana Jessica Di Paola, Antonio De Leo, Thais Maloberti, Sara Coluccelli, Laura Poppi, Andrea Repaci, Erica Solaroli, Stefania Damiani, Stefano Chillotti, Federico Chiarucci, Kerry J. Rhoden, Dario de Biase, Giovanni Tallini
Abstract
Thyroid cancer is the most prevalent endocrine malignancy. Distinct genetic alterations drive the development and progression of thyroid tumors of follicular cells with remarkable genotype-phenotype correlation. In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations. Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling. Understanding the genetic landscape of thyroid carcinoma of follicular cells is essential to optimize clinical management and to identify molecular targets to treat cases with aggressive disease refractory to standard radioactive iodine therapy. What follows is a comprehensive and updated outline of the main somatic genetic and molecular alterations in thyroid carcinoma of follicular cells.