Case Report of CCDC149–ALK Fusion: A Novel Genetic Alteration and a Clinically Relevant Target in Metastatic Papillary Thyroid Carcinoma

Abstract

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, usually with an indolent course. ALK fusions are rare in PTC but may give rise to a more aggressive behavior. We report a novel ALK fusion, CCDC149-ALK, not previously described in PTC, detected by next generation sequencing (NGS) in a 30 year-old woman with progressive, widely metastatic radioiodine-refractory (RAIR) disease to lung, muscle, and brain. The patient was started on alectinib, a second-generation ALK inhibitor. Within 8 weeks, her palpable disease had completely regressed, and the serum thyroglobulin decreased dramatically. Restaging imaging demonstrated an objective partial response. Our case highlights the role of ALK fusions in thyroid cancer and highlights its clinical significance in PTC. We recommend deep mutational sequencing in BRAFV600E-negative, RAIR PTC to identify targetable genetic alterations, including gene fusions, that may result in dramatic therapeutic benefits.