Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

• Published in: Journal of Korean medical science Vol. 29; no. 8; pp. 1054 - 1060
• Main Authors: Cho, Uiju, Oh, Woo Jin, Bae, Ja Seong, Lee, Sohee, Lee, Young Sub, Park, Gyeong Sin, Lee, Youn Soo, Jung, Chan Kwon
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Academy of Medical Sciences 01.08.2014; 대한의학회
• Subjects: Base Sequence; Biomarkers, Tumor - genetics; Female; Genetic Markers - genetics; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Humans; Incidence; Male; Middle Aged; Molecular Sequence Data; Mutation - genetics; Original; Polymorphism, Single Nucleotide - genetics; Prevalence; Proto-Oncogene Proteins B-raf - genetics; Rare Diseases - epidemiology; Rare Diseases - genetics; Republic of Korea - epidemiology; Risk Factors; Thyroid Neoplasms - epidemiology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; 의학일반; Republic of Korea; Biomarkers; Pathology; Thyroid Neoplasms; BRAF; Mutation
• ISSN: 1011-8934; 1598-6357; 1598-6357
• DOI: 10.3346/jkms.2014.29.8.1054

The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>G mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>G mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma. [Corrected]