Frequent BRAFV600E and Absence of TERT Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan

Naoki Oishi, Tetsuo Kondo, Tadao Nakazawa, Kunio Mochizuki, Tomohiro Inoue, Kazunari Kasai, Ippei Tahara, Tomonori Yabuta, Mitsuyoshi Hirokawa, Akira Miyauchi, Ryohei Katoh

Pediatric papillary thyroid carcinoma (PTC) has unique features but requires further genetic investigation. Moreover, there has been increasing concern about the risk for pediatric PTC in Japan after the Fukushima accident. This study aims to evaluate the frequencies of BRAF and TERT promoter mutations and to examine their significance in non-radiation-associated pediatric PTCs in Japan. We enrolled 81 pediatric PTC patients aged ≤20 years. The control group included 91 adult PTCs from patients >20 years old. BRAF and TERT mutations were analyzed by allele-specific-PCR and/or Sanger sequencing. Compared with adult PTCs, pediatric PTCs exhibited larger tumor size, more frequent lymph node metastasis, and less classical histology. The prevalence of BRAF (V600E) in pediatric PTCs was 54% and significantly lower than that in adults of 85%. In the pediatric PTCs, BRAF (V600E) was positively associated with older age, classical histology, and the lymph node metastasis but independent from other clinicopathological factors. TERT mutations were identified in 13% of adults and in none of the pediatric PTCs. In conclusion, pediatric PTCs are characterized by more advanced clinicopathological features, lower BRAF (V600E) frequency, and absence of TERT mutation. The BRAF (V600E) frequency in this study is similar to the reported BRAF (V600E) frequency in the ultrasonographically screened pediatric PTCs in Fukushima.