Clinicopathological Features of Rare BRAF Mutations in Korean Thyroid Cancer Patients

Abstract

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

Molecular cytopathology for thyroid nodules: A review of methodology and test performance

“…Reclassification of noninvasive FVPTCs as neoplasms with low malignant potential rather than carcinomas would reduce the prevalence of malignancy among indeterminate FNAs, which would in turn affect the predictive values of these tests . Furthermore, the genotype of FVPTCs appears to correlate with biologic behavior; noninvasive FVPTCs tend to harbor RAS mutations, BRAF K601E mutations, and PAX8/PPARγ fusions, whereas invasive FVPTCs demonstrate an increased rate of BRAF V600E mutations . Therefore, test panels that preoperatively distinguish between “ RAS ‐like” and “ BRAF V600E‐like” molecular profiles will become increasingly relevant in guiding appropriate treatment options; lobectomy may be appropriate initial management for the former, whereas total thyroidectomy would be indicated for the latter (Fig.…”

Analysis of RAS mutation in thyroid nodular hyperplasia and follicular neoplasm in a Korean population

“…[4][5][6] RAS mutations are the second most common genetic alteration in thyroid tumours. [4][5][6] RAS mutations are the second most common genetic alteration in thyroid tumours.…”

“…The BRAF V600E mutation is the most common genetic alteration in thyroid tumorigenesis and has been observed in 29%-83% of papillary thyroid carcinomas (PTCs). [4][5][6] RAS mutations are the second most common genetic alteration in thyroid tumours. Recent studies have reported that 10%-20% of PTCs and 40%-50% of FTCs harbour RAS mutations.…”

Impact of NRAS Mutations on the Diagnosis of Follicular Neoplasm of the Thyroid

“…The BRAF V600E mutation is the most common genetic alteration in thyroid tumorigenesis and has been observed in ~29–83% of papillary thyroid carcinoma (PTC) [5–7]. RAS mutations are the second most common genetic alteration in thyroid tumors.…”