We examined IQGAP1 copy gain and its relationship with clinicopathologic outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process. We found IQGAP1 copy number (CN) gain ?3 in 1 of 30 (3%) of benign thyroid tumor, 24 of 74 (32%) follicular variant papillary thyroid cancer (FVPTC), 44 of 107 (41%) follicular thyroid cancer (FTC),, 8 of 16 (50%) tall cell papillary thyroid cancer (PTC), and 27 of 41 (66%) anaplastic thyroid cancer, in increasing order of invasiveness of these tumors. A similar tumor distribution trend of CN ?4 was also seen. IQGAP1 copy gain was positively correlated with IQGAP1 protein expression. It was significantly associated with extrathyroidal and vascular invasion of FVPTC and FTC and, remarkably, a 50%-60% rate of multifocality and recurrence of BRAF mutation-positive PTC (P = 0.01 and 0.02, respectively). The siRNA knockdown of IQGAP1 dramatically inhibited thyroid cancer cell invasion and colony formation. Co-immunoprecipitation assay showed direct interaction of IQGAP1 with E-cadherin, a known invasion-suppressing molecule, which was upregulated when IQGAP1 was knocked down. IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and represents a useful prognostic marker and therapeutic target for this and other cancers.Les présents inventeurs ont étudié le gain en nombre de copies dIQGAP1 et sa relation avec les issues clinicopathologiques du cancer de la thyroïde et ils ont étudié son rôle dans linvasion cellulaire ainsi que les molécules impliquées dans le processus. Ils ont découvert un gain en nombre de copies (NC) ?3 dans 1 tumeur bénigne de la thyroïde sur 30 (3 %), dans 24 cancers papillaires de la thyroïde, variante folliculaire (FVPTC), sur 74 (32 %), dans 44 cancers folliculaires de la thyroïde (FTC) sur 107 (41 %), dans 8 cancers papillaires de la thyroïde à grandes cellules (PTC) sur 16 (50 %), et dans 27 cancers anaplasiques de la thyroï
