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• W2157960706 abstract "BRAFV600E is considered a primary event, a negative prognostic marker, and a site for pharmacological intervention in papillary thyroid carcinoma (PTC). We asked whether BRAFV600E can occur as a subclonal event in PTC and whether this and other oncogenes can coexist in the same tumor. We determined by pyrosequencing the percentage of mutant BRAF, NRAS, and KRAS alleles in a series of conventional PTC. We also analyzed the BRAF mutation status in PTC cell clones in culture. BRAFV600E alleles were present in 41 of 72 PTC (56.9%) in the range 44.7 to 5.1% of total BRAF alleles. In four PTC samples, mutant BRAF alleles were about 50%, being therefore compatible with a clonal heterozygous mutation. In 27 PTC samples, BRAFV600E alleles were in the range of 25 to 5.1%. This finding was confirmed after exclusion of the presence of a large contamination by lymphoreticular cells and by the analysis of PTC cells selected by laser capture. Analysis of clones derived from a single cell confirmed the presence of two distinct PTC populations with wild-type or mutated BRAF. Simultaneous subclonal BRAF and KRAS mutations were demonstrated in two PTC. These data demonstrate that clonal BRAFV600E is a rare occurrence in PTC, although frequently this cancer consists of a mixture of tumor cells with wild-type and mutant BRAF. These results suggest that BRAF mutation in PTC is a later subclonal event, its intratumoral heterogeneity may hamper the efficacy of targeted pharmacotherapy, and its association with a more aggressive disease should be reevaluated." @default.
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• W2157960706 date "2012-02-01" @default.
• W2157960706 modified "2023-09-27" @default.
• W2157960706 title "The Primary Occurrence of<i>BRAF^V600E</i>Is a Rare Clonal Event in Papillary Thyroid Carcinoma" @default.
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• W2157960706 doi "https://doi.org/10.1210/jc.2011-0618" @default.
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