Expression analysis of mouse thyroid tumors

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. We have engineered the first mouse model of ATC by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion and distant metastases. We have performed expression profiling of thyroids from control, single mutants, compound mutants, follicular tumors from Pten-/- mice and [Pten-/-,KrasG12D] mice, and anaplastic tumors from Pten, p53-/- mice.