CONTEXT: For patients with metastatic papillary thyroid carcinoma (PTC) 
refractory to radioactive iodine (RAI) treatment, systemic chemotherapy has 
limited efficacy. Such tumors frequently harbor BRAF V600E, and this alteration 
may predict responsiveness to vemurafenib treatment.
OBJECTIVE: We report a metastatic PTC patient refractory to RAI treatment that 
underwent genomic profiling by next-generation sequencing. The sole genomic 
alteration identified was BRAF V600E on a near diploid genome with trisomy 1q. 
With vemurafenib treatment, the patient experienced a dramatic radiographic and 
clinical improvement, with the duration of an ongoing antitumor response 
exceeding 23 months.
DESIGN: Hybridization capture of 3,769 exons of 236 cancer-related genes and the 
introns of 19 genes frequently rearranged in cancer was applied to >50 ng of DNA 
extracted from a formalin-fixed, paraffin-embedded biopsy of a lymph node 
containing metastatic PTC and was sequenced to a high, uniform coverage of ×616.
RESULTS: A BRAF V600E alteration was identified with no other somatic genomic 
alterations present within a near diploid tumor genome. The patient initially 
received vemurafenib at 960 mg twice daily that was reduced to 480 mg twice 
daily due to rash and diarrhea and has experienced an ongoing antitumor response 
exceeding 23 months by both PET-CT and dedicated CT imaging.
CONCLUSIONS: Genomic profiling in metastatic, RAI-refractory PTC can reveal a 
targetable BRAF V600E alteration without compounding somatic alterations, and 
such patients may derive a more prolonged benefit from vemurafenib treatment. 
Prospective clinical trials are ongoing to confirm our preliminary observation.