Frequent BRAFV600Eand Absence of TERT Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan.
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 BRAFV600Ein pediatric PTCs was 54% and significantly lower than that in adults of 85%. In the pediatric PTCs, BRAFV600Ewas 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 BRAFV600Efrequency, and absence of TERT mutation. The BRAFV600Efrequency in this study is similar to the reported BRAFV600Efrequency in the ultrasonographically screened pediatric PTCs in Fukushima.
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Naoki
N
Oishi
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Tetsuo
T
Kondo
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Tadao
T
Nakazawa
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Kunio
K
Mochizuki
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Tomohiro
T
Inoue
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Kazunari
K
Kasai
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan.
Ippei
I
Tahara
Department of Surgery, Kuma Hospital, Kobe, Hyogo, 650-0011, Japan.
Tomonori
T
Yabuta
Department of Diagnostic Pathology, Kuma Hospital, Kobe, Hyogo, 650-0011, Japan.
Mitsuyoshi
M
Hirokawa
Department of Surgery, Kuma Hospital, Kobe, Hyogo, 650-0011, Japan.
Akira
A
Miyauchi
Department of Pathology, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan. rkatoh@yamanashi.ac.jp.
Ryohei
R
Katoh
D000293:Adolescent; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase
Adult; BRAF; Mutation; Papillary thyroid carcinoma; Pediatric; TERT