A Novel ALK Fusion in Pediatric Medullary Thyroid Carcinoma

Thyroid. 2019 Nov;29(11):1704-1707. doi: 10.1089/thy.2019.0041.


Medullary thyroid carcinoma (MTC) is most commonly associated with RET gene mutations. ALK fusions have rarely been described, although not previously in pediatrics and not previously partnered with CCDC6 in MTC or any other cancer. A 10-year-old boy with progressive stridor was found to have metastatic MTC, including lung, lymph node, and adrenal metastases. Baseline calcitonin was 6703 pg/mL. While molecular testing was pending, he was treated empirically with the investigational selective RET inhibitor, LOXO-292, without improvement. Molecular testing revealed a novel CCDC6-ALK fusion. His therapy was changed to crizotinib and then to alectinib for improved tolerability. Calcitonin decreased to 663 pg/mL after 6 days of ALK inhibition. He remains on alectinib with ongoing response. A novel CCDC6-ALK fusion has now been implicated in a pediatric case of metastatic MTC. This fusion has profound clinical sensitivity to ALK inhibitors. This report expands the spectrum of ALK fusions seen in MTC, including the first pediatric case of ALK translocated MTC. This novel fusion with CCDC6 has not previously been reported in other human cancers. Given the dramatic response to ALK inhibition in this case, identifying patients with ALK fusion MTC has important therapeutic implications.

Keywords: ALK; CCDC6; alectinib; medullary thyroid carcinoma; pediatric.

Publication types

  • Case Reports

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics*
  • Antineoplastic Agents / therapeutic use
  • Calcitonin / metabolism
  • Carbazoles / therapeutic use
  • Carcinoma, Neuroendocrine / genetics*
  • Child
  • Cytoskeletal Proteins / genetics
  • Gene Fusion / genetics*
  • Humans
  • Male
  • Molecular Diagnostic Techniques
  • Mutation
  • Neoplasm Metastasis
  • Piperidines / therapeutic use
  • Thyroid Neoplasms / genetics*
  • Treatment Outcome


  • Antineoplastic Agents
  • CCDC6 protein, human
  • Carbazoles
  • Cytoskeletal Proteins
  • Piperidines
  • Calcitonin
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • alectinib

Supplementary concepts

  • Thyroid cancer, medullary