Mutational Patterns and Novel Mutations of the <i>BRAF</i> Gene in a Large Cohort of Korean Patients with Papillary Thyroid Carcinoma

Jung, Chan-Kwon; Im, Soyoung; Kang, Yeo-Ju; Lee, Hyoungnam; Jung, Eun-Young; Kang, Chang Suk; Bae, Ja Seong; Choi, Yeong-Jin

doi:10.1089/thy.2011.0123

Cited by 52 publications

(27 citation statements)

References 23 publications

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“…Among those, the most common mutation is a point mutation that involves a thymine to adenine substitution at position c.1799 of the BRAF gene, which results in a valine-to-glutamate substitution at amino acid codon 600 (p.Val600Glu; V600E). BRAF V600E represents almost 99% of all BRAF mutations in thyroid cancer (2). We previously reported that BRAF mutations were found in 835 (80.2%) of 1,041 Korean patients with PTC (2).…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

Cho

Bae

et al. 2014

J Korean Med Sci

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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>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C 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.Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

Cho

Bae

et al. 2014

J Korean Med Sci

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“…BRAF mutations are the most common mutations in PTCs, and BRAF V600E constitutes 99% of all BRAF mutations 37. The increase in prevalence of BRAF mutations in accordance with iodine supplementation and increase in proportion of PTCs have been reported in different geographical areas 38, 39, 40.…”

Section: Discussionmentioning

confidence: 98%

Genetic alterations of differentiated thyroid carcinoma in iodine‐rich and iodine‐deficient countries

et al. 2016

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BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine‐rich country (Japan) and an iodine‐deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele‐specific polymerase chain reaction (AS‐PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS,HRAS, and KRAS), and RT‐PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E,RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine‐rich and iodine‐deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer.

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“…Finkelstein et al21 demonstrated a significant association between the presence of the BRAF mutation and fibrosis, desmoplastic stromal reaction, and infiltrating tumor borders. The BRAF mutation occurs commonly in Korean patients with PTC, ranging in frequency from 52% to 87% of all cases 8. The prevalence of the BRAF mutation worldwide is reported to be as high as 80% to 100% in TCVPTCs 29.…”

Section: Discussionmentioning

confidence: 99%

“…The tissue sections were manually microdissected to enrich for tumor cells. We screened for mutations in exon 15 of the BRAF gene using polymerase chain reaction amplification and direct DNA sequencing, as described previously 8,22…”

Section: Methodsmentioning

confidence: 99%

“…The incidence of TCVPTC ranges from 4% to 17% of all PTCs, and its disease-free 10-year survival rate is believed to be 10% to 15% lower than that of classic PTC 5,6. The incidence of this disease in Korea has been reported to be up to 5%, although there are limited existing data 7,8. Some studies suggest that TCV PTC is still under-diagnosed worldwide 3,4,5,9,10.…”

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Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features

Lee

Cho

et al. 2014

Korean J Pathol

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BackgroundThe tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF).MethodsWe retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having <10%, 10-50%, and ≥50% tall cells, respectively.ResultsTCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (≤1.0 cm in size).ConclusionsClassic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.

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Mutational Patterns and Novel Mutations of the BRAF Gene in a Large Cohort of Korean Patients with Papillary Thyroid Carcinoma

Cited by 52 publications

References 23 publications

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

Genetic alterations of differentiated thyroid carcinoma in iodine‐rich and iodine‐deficient countries

Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features

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