Our findings identify a novel CREB3L2-PPARgamma gene fusion mutation in thyroid carcinoma and reveal a thyroid signaling pathway that is regulated by intramembrane proteolysis and disrupted in cancer..     ///    "Here, we report our discovery of a novel CREB3L2-PPARgamma fusion mutation in thyroid carcinoma with t(3;7)(p25;q34), showing that a family of somatic PPARgamma fusion mutations exist in thyroid cancer. "    ///    "Nuclear CREB3L2 stimulated transcription 8-fold from the EVX1 cyclic AMP (cAMP) response element in the absence of cAMP, whereas CREB3L2-PPARgamma inhibited transcription 6-fold from EVX1 in the same experiments. "    ///    "CREB3L2-PPARgamma also inhibited 4-fold the expression of thyroglobulin, a native cAMP-responsive gene, in primary thyroid cells treated with thyroid-stimulating hormone. "    ///    "Engineered overexpression of CREB3L2-PPARgamma induced proliferation by 40% to 45% in primary human thyroid cells, consistent with a dominant oncogenic mechanism. "    ///    CREB3L2-PPARgamma was detected in <3% of thyroid follicular carcinomas.     ///    CREB3L2-PPARgamma fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis..     ///    The CREB3L2-PPARgamma fusion encodes a CREB3L2-PPARgamma fusion protein that is composed of the transactivation domain of CREB3L2 and all functional domains of PPARgamma1. 