Expanding the Spectrum of <i>BRAF</i> Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre

Expanding the Spectrum of <i>BRAF</i> Non-V600E Mutations in Thyroid Nodules: Evidence-Based Data from a Tertiary Referral Centre

The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. <i>BRAF</i> alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechani...

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Bibliographic Details
Main Authors: Antonio De Leo, Daniela Serban, Thais Maloberti, Viviana Sanza, Sara Coluccelli, Annalisa Altimari, Elisa Gruppioni, Federico Chiarucci, Angelo Gianluca Corradini, Andrea Repaci, Alessandra Colapinto, Margherita Nannini, Maria A. Pantaleo, Dario de Biase, Giovanni Tallini
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
thyroid tumors
<i>BRAF</i>
mutation
next-generation sequencing
noncanonical mutation
Online Access:https://www.mdpi.com/1422-0067/24/4/4057
Description
Summary:The BRAF p.V600E mutation represents the most specific marker for papillary thyroid carcinoma and is potentially related to aggressive behavior and persistent disease. <i>BRAF</i> alterations other than the p.V600E are less common in thyroid carcinoma and represent an alternative mechanism of BRAF activation with unclear clinical significance. The study aims to describe the frequency and clinicopathologic characteristics of <i>BRAF</i> non-V600E mutations in a large cohort (1654 samples) of thyroid lesions characterized by next-generation sequencing. <i>BRAF</i> mutations have been found in 20.3% (337/1654) of thyroid nodules, including classic (p.V600E) mutation in 19.2% (317/1654) of samples and non-V600E variants in 1.1% of cases (19/1654). BRAF non-V600E alterations include 5 cases harboring p.K601E, 2 harboring p.V600K substitutions, 2 with a p.K601G variant, and 10 cases with other <i>BRAF</i> non-V600E alterations. <i>BRAF</i> non-V600E mutations have been reported in one case of follicular adenoma, three cases of conventional papillary thyroid carcinoma, eight cases of follicular variant of papillary carcinomas, one case of columnar cell variant papillary thyroid carcinoma, one case of oncocytic follicular carcinoma, and two bone metastasis of follicular thyroid carcinoma. We confirm that <i>BRAF</i> non-V600E mutations are uncommon and typically found in indolent follicular-patterned tumors. Indeed, we show that <i>BRAF</i> non-V600E mutations can be found in tumors with metastatic potential. However, in both aggressive cases, the <i>BRAF</i> mutations were concomitant with other molecular alterations, such as <i>TERT</i> promoter mutation.
ISSN:1661-6596
1422-0067

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