The initiation of thyroid cancer is often triggered by a genetic mutation in the phosphortidylinositol-3 kinase (PI3K) or mitogen-activated protein kinase (MAPK) pathway, such as <i>RAS</i> and <i>BRAF</i>, or by the rearrangement of growth factor receptor tyrosine kinase genes such as <i>RET/PTC</i>.
Recent novel and promising findings include additional abnormalities in key pathways associated with thyroid tumorigenesis (RET-Ras-BRAF-MEK; RET-beta-cateinin; TRK-PI3K-AKT; and MDM-p53-PTEN), single-nucleotide polymorphisms associated with thyroid cancer susceptibility, epigenetic silencing, alternative splicing, and gene expression abnormalities.
This provides an explanation for the reciprocal relationship of rs17849071G/T with FTC, since PIK3CA amplification is an important oncogenic mechanism in thyroid cancer, particularly FTC.
Mutations in the PIK3CA have also been identified in thyroid cancers and, although relatively common in anaplastic thyroid carcinoma, are uncommon in PTC.
Initiation and progression of thyroid cancer involves multiple genetic and epigenetic alterations, of which mutations leading to the activation of the MAPK and PI3K-AKT signaling pathways are crucial.
Thyroid cancer (TC) is frequently associated with BRAF or RAS oncogenic mutations and RET/PTC rearrangements, with aberrant RAF-MEK-ERK and/or PI3K pathway activation.