Frequent BRAF V600E and Absence of TERT Promoter Mutations Characterize Sporadic Pediatric Papillary Thyroid Carcinomas in Japan
- 329 Downloads
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.
KeywordsPapillary thyroid carcinoma Pediatric Adult Mutation BRAF TERT
We thank Ms. Wakaba Iha, Ms. Miyuki Ito, Ms. Mikiko Yoda, and Mr. Yoshihito Koshimizu for technical support and Ms. Kayoko Kono for executive assistance.
Compliance with Ethical Standards
This study was funded by Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number 25293087 and 90,623,661).
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures in this study were in accordance with the ethical standards of the institutional research committee. For this type of study, formal consent is not required.
- 20.Onder S, Ozturk Sari S, Yegen G, Sormaz IC, Yilmaz I, Poyrazoglu S, et al. Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF V600E Harboring Pediatric Papillary Thyroid Carcinomas. Endocr Pathol 27:153–161, 2016CrossRefPubMedGoogle Scholar
- 27.Mitsutake N, Fukushima T, Matsuse M, Rogounovitch T, Saenko V, Uchino S, et al. BRAFV600E mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl. Sci Rep 16976, 2015Google Scholar
- 29.LiVolsi VA, Albores-Saavedra J, Asa SL, Baloch ZW, Sobrinho-Simões M, Wenig B et al. Papillary carcinoma, in DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds): Pathology and genetics of tumours of endocrine organs. Lyon: IARC; 2004. pp 57–66.Google Scholar
- 33.Xu B, Yoshimoto K, Miyauchi A, Kuma S, Mizusawa N, Hirokawa M, et al. Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol. 199:58–67, 2003.CrossRefPubMedGoogle Scholar
- 43.Gouveia C, Can NT, Bostrom A, Grenert JP, van Zante A, Orloff LA. Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience. JAMA Otolaryngol Head Neck Surg 139:1164–1170, 2013CrossRefPubMedGoogle Scholar