title: Mutational patterns and novel mutations of the BRAF gene in a large cohort of Korean patients with papillary thyroid carcinoma.
abstract: BACKGROUND
  BRAF mutation is the most common genetic event in papillary thyroid carcinoma (PTC); however, the prevalence and patterns of the mutation vary worldwide. We investigated the frequency and type of BRAF mutations based on the histologic subtypes in a large cohort of Korean patients with PTC.
  
  
  METHODS
  A total of 1041 consecutive PTCs were classified according to histologic subtypes. BRAF mutations were examined by denaturing high-performance liquid chromatography and direct sequencing. Rare complex mutations were confirmed by molecular cloning of polymerase chain reaction amplicons and sequencing of the products.
  
  
  RESULTS
  BRAF mutations were found in 839 (80.6%) of 1041 patients with PTC. The histologic subtype-specific prevalence of BRAF mutation was as follows: 85.3% (249/292) were classic, 45.8% (11/24) were follicular, 79.9% (576/721) were microcarcinoma, and 75.0% (3/4) were other variants. In addition to the usual c.1799T>A mutation, we identified other four mutation types: c.[1795_1796insA;1770_1795dup26], c.[1742-10T>C;1799T>A] and c.[1796C>G;1799T>A], and c.1799_1800TG>AA, respectively. The former three were novel mutations in thyroid tumors. Within the series of microcarcinoma variants, the BRAF mutation rate was lower in tumors with follicular morphology than those with nonfollicular types (66.7% vs. 80.9%, p=0.0145).
  
  
  CONCLUSIONS
  Out of 1041 Korean patients with PTC, 0.4% had rare types of BRAF mutation and three new somatic mutations were identified. The BRAF mutation rate was quite low in PTC with follicular morphology regardless of tumor size. However, the prevalence of BRAF mutation in microcarcinoma and follicular variants of PTC is relatively high in Korea and its analysis may be clinically useful for managing the patients.
authors.affiliation: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chan-Kwon
authors.initials: CK
authors.lastname: Jung
authors.forename: So-Young
authors.initials: SY
authors.lastname: Im
authors.forename: Yeo-Ju
authors.initials: YJ
authors.lastname: Kang
authors.forename: Hyoungnam
authors.initials: H
authors.lastname: Lee
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Jung
authors.forename: Chang-Suk
authors.initials: CS
authors.lastname: Kang
authors.forename: Ja-Seong
authors.initials: JS
authors.lastname: Bae
authors.forename: Yeong-Jin
authors.initials: YJ
authors.lastname: Choi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D056910:Republic of Korea; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf