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首页> 外文期刊>Hormone and Metabolic Research >Lack of correlation between BRAF V600E mutational status and the expression profile of a distinct set of miRNAs in papillary thyroid carcinoma.
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Lack of correlation between BRAF V600E mutational status and the expression profile of a distinct set of miRNAs in papillary thyroid carcinoma.

机译：在甲状腺乳头状癌中，BRAF V600E突变状态与一组不同的miRNA的表达谱之间缺乏相关性。

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摘要

Recent studies demonstrated a significant upregulation of distinct microRNAs (miRNAs), small endogenous RNAs that regulate gene expression, in papillary thyroid carcinoma (PTC). In the pathogenesis of PTC the T1799A (V600E) BRAF mutation is the most common genetic alteration leading to a constitutive activation of the MAPK pathway. The aim of the present study was to elucidate a possible correlation between BRAF mutational status and a distinct miRNA expression profile. In a series of 221 PTC we determined the BRAF V600E mutational status using DNA-sequencing and correlated the occurrence of the mutation with a variety of clinicopathologcial data. The miRNA expression profile of five selected subtypes (miRNA-146b, -181b, -21, -221, -222) in two matched cohorts of BRAF positive (n=28) and wildtype cases (n=26) was examined by RT-PCR TaqMan miRNA assay. The BRAF V600E mutation was significantly found in PTCs with extrathyroidal extension (p <0.001). Among them, V600E was even significantly associated with smaller tumour size of 1 cm or less (microcarcinomas; p<0.003) and the follicular (p=0.017) and tall cell variant (p=0.015). By calculating relative changes in miRNA gene expression no differences in fold changes could be detected between BRAF positive and wildtype PTC suggesting that BRAF has no regulatory influence on the expression of the five examined miRNAs. However, our study confirmed the diagnostic utility of this distinct set of miRNAs to detect PTC by significant fold changes in at least 3 miRNAs (miRNA-146b, -221, -222) irrespective of its histological variant.
机译：最近的研究表明，在甲状腺乳头状癌（PTC）中，独特的微小RNA（miRNA）是一种微小的内源性RNA，可调节基因表达，从而显着上调。在PTC的发病机理中，T1799A（V600E）BRAF突变是导致MAPK途径组成型激活的最常见的遗传改变。本研究的目的是阐明BRAF突变状态与不同的miRNA表达谱之间可能存在的相关性。在一系列221 PTC中，我们使用DNA测序确定了BRAF V600E的突变状态，并将突变的发生与多种临床病理学数据相关联。通过RT-PCR检测了两个配对的BRAF阳性（n = 28）和野生型病例（n = 26）的匹配队列中的五个选定亚型（miRNA-146b，-181b，-21，-221，-222）的miRNA表达谱PCR TaqMan miRNA分析。在伴有甲状腺外延伸的PTC中发现BRAF V600E突变（p <0.001）。其中，V600E甚至与1 cm或更小的较小肿瘤尺寸（微癌; p <0.003）以及卵泡（p = 0.017）和高细胞变体（p = 0.015）显着相关。通过计算miRNA基因表达的相对变化，在BRAF阳性和野生型PTC之间未检测到倍数变化的差异，这表明BRAF对五个检测到的miRNA的表达没有调节作用。但是，我们的研究证实了这组独特的miRNA的诊断功能，可通过至少3个miRNA（miRNA-146b，-221，-222）的显着倍数变化来检测PTC，而不论其组织学变异如何。

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