CCDC6, the Coiled Coil Domain Containing 6 gene, was initially found as part of a tumorigenic DNA fusion with the RET receptor's tyrosine kinase following a chromosome 10 inversion [1]. It plays a proper role in sustaining DNA damage checkpoints in response to DNA damage, acting as a tumor suppressor gene in the DNA repair system [1,2].

CCDC6-RET fusion is common in papillary thyroid cancer, and CCDC6-RET transgenic mice develop thyroid hyperplasia associated with enhanced CREB1 activity, suggesting a promoting role of CCDC6 functional impairment in thyroid papillary carcinomas [5,6]. In high-grade urothelial bladder cancer, deficiency of CCDC6 determines PARP-inhibitor sensitivity [4]. Also, FGFR2-CCDC6 fusion gene promotes cell proliferation by excessively activating the AKT and ERK signaling pathway downstream of FGFR2 [3].

In conclusion, CCDC6 is crucial in maintaining DNA damage checkpoints. Its involvement in various fusion genes, especially in cancers like thyroid and urothelial bladder cancer, highlights its significance in disease development. Studies using transgenic mouse models have provided insights into its role in cancer-related biological processes, potentially guiding future therapeutic strategies.