The genetic landscape of benign thyroid nodules revealed by whole exome and transcriptome sequencing.
The genetic landscape of benign thyroid nodules revealed by whole exome and transcriptome sequencing.
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全外显子组和转录组测序揭示良性甲状腺结节的遗传图谱
DOI：
10.1038/ncomms15533
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发表时间：
2017-06-05
影响因子：
16.6
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Ye L;Zhou X;Huang F;Wang W;Qi Y;Xu H;Yang S;Shen L;Fei X;Xie J;Cao M;Zhou Y;Zhu W;Wang S;Ning G;Wang W
甲状腺良性结节，特别是腺瘤样结节，是最常见的增生性病变之一，其基因组变异研究较少。在这里，我们展示了腺瘤样结节伴或不伴甲状腺乳头状癌（PTC）的全外显子组测序和/或转录组测序数据。BRAF（22/32）的体细胞突变仅见于PTC，SPOP（4/38）、ZNF 148（6/38）和EZH 1（3/38）的突变在腺瘤样结节中富集。在一个扩大的腺瘤样结节队列（n=259）中，24.3%的腺瘤样结节中发现了SPOPP 94 R、EZH 1 Q571和ZNF 148的互斥突变。腺瘤样结节很少有重叠突变和独特的基因表达模式与他们的巧合PTC。系统发育树分析揭示了PTC独立于其匹配的良性结节进化。我们的研究结果表明，良性结节具有独特的分子特征，不同于PTC，并提供基因组证据的传统信念，PTC和良性结节有独立的起源。
The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied. Here, we show whole-exome sequencing and/or transcriptome sequencing data on adenomatoid nodules with or without coincidental papillary thyroid carcinoma (PTC). Somatic mutation ofBRAF(22/32) is only detected in PTC, while mutations inSPOP(4/38),ZNF148(6/38) andEZH1(3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusiveSPOPP94R,EZH1Q571RandZNF148mutations are identified in 24.3% of them. Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC. Phylogenetic tree analysis uncovers that PTCs evolved independently from their matched benign nodules. Our findings reveal that benign nodules possess a unique molecular signature that differs from PTC and provide genomic evidence for the conventional belief that PTC and benign nodules have independent origin.