Identification of Novel Oncogenic Mutations in Thyroid Cancer

Thyroid cancer patients frequently have favorable outcomes. However, a small subset develops aggressive disease refractory to traditional treatments. Therefore, we sought to characterize oncogenic mutations in thyroid cancers to identify novel therapeutic targets that may benefit patients with advanced, refractory disease.

Data on 239 thyroid cancer specimens collected between January 2009 and September 2014 were obtained from the Dana Farber/Brigham and Women's Cancer Center. The tumors were analyzed with the OncoMap-4 or OncoPanel high-throughput genotyping platforms that survey up to 275 cancer genes and 91 introns for DNA rearrangement.

Of the 239 thyroid cancer specimens, 128 (54%) had oncogenic mutations detected. These 128 tumors had 351 different mutations detected in 129 oncogenes or tumor suppressors. Examination of the 128 specimens demonstrated that 55% (n = 70) had 1 oncogenic mutation, and 45% (n = 48) had more than 1 mutation. The 351 oncogenic mutations were in papillary (85%), follicular (4%), medullary (7%), and anaplastic (4%) thyroid cancers. Analysis revealed that 2.3% (n = 3 genes) of the somatic gene mutations were novel. These included AR (n = 1), MPL (n = 2), and EXT2 (n = 1), which were present in 4 different papillary thyroid cancer specimens. New mutations were found in an additional 13 genes known to have altered protein expression in thyroid cancer: BLM, CBL, CIITA, EP300, GSTM5, LMO2, PRAME, SBDS, SF1, TET2, TNFAIP3, XPO1, and ZRSR2.

This analysis revealed that several previously unreported oncogenic gene mutations exist in thyroid cancers and may be targets for the development of future therapies. Further investigation into the role of these genes is warranted.