Genetic Changes Affecting MAPK and PI3K Pathways in Thyroid Cancer.

Somatic or epigenetic changes in genes encoding the components of the MAPK and PI3K pathways (star) lead to constitutive activation of these classical receptor tyrosine kinase (RTK) signaling pathways. These genetic changes include a BRAF mutation, RAS mutation, and RET/PTC gene fusion that constitutively activate the MAPK pathway. Genetic changes that lead to activation of the PI3K pathway include RAS mutation, PTEN mutation or hypermethylation, and AKT1 mutation. Once permanently activated these pathways play a fundamental mechanistic role in thyroid tumorigenesis.