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  • Title: Circulating Tumor DNA Harboring the BRAFV600E Mutation May Predict Poor Outcomes of Primary Papillary Thyroid Cancer Patients.
    Author: Sato A, Tanabe M, Tsuboi Y, Niwa T, Shinozaki-Ushiku A, Seto Y, Murakami Y.
    Journal: Thyroid; 2021 Dec; 31(12):1822-1828. PubMed ID: 34541884.
    Abstract:
    Background: The significance of circulating tumor DNA (ctDNA) in primary papillary thyroid cancer (PTC) is yet to be well established. This study aimed to clarify whether ctDNA carrying the BRAFV600E mutation in plasma from primary PTC patients before and after surgery can predict outcomes. Methods: Twenty-two primary PTC patients without distant metastasis, who underwent surgical resection at the University of Tokyo Hospital, were eligible for this study. Genomic DNA of the primary tumor was extracted from formalin-fixed and paraffin-embedded specimens, and the BRAFV600E mutation was detected by droplet digital polymerase chain reaction (ddPCR). Pre- and postsurgery ctDNAs were extracted from matched plasma samples obtained from 22 patients and analyzed for the BRAFV600E mutation using ddPCR. Results: The BRAFV600E mutation was detected in 16 of 22 (73%) primary tumors. Five of 16 (31%) cases carrying the BRAFV600E mutation in their tumors showed the identical mutation in presurgery plasma. Extrathyroidal extension of the primary tumor correlated significantly with the BRAFV600E mutation in presurgery ctDNA (p = 0.025). In the five patients carrying the BRAFV600E mutation in presurgery ctDNA, the fractional abundance of the BRAFV600E alleles to the total BRAF alleles in the primary tumor was significantly higher than that in the 11 patients without mutated BRAF in presurgery ctDNA (mean, 34% vs. 17%) (p < 0.01). Moreover, one patient with the mutated BRAFV600E in the primary tumor showed the identical mutation not in presurgery ctDNA but in postsurgery ctDNA. This patient had regional lymph node recurrence six months after surgery. Conclusions: Presurgery ctDNA with the BRAFV600E mutation was detected in 31% of cases with primary PTCs carrying the identical mutation. Detection of the BRAFV600E mutation in presurgery plasma can provide information on the increased fractional abundance of the mutated BRAFV600E alleles and local progression of the primary tumor. Furthermore, the fractional abundance of the mutated BRAFV600E in postsurgery ctDNA might predict PTC recurrence.
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