Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-institute for Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China.
Department of Laboratory Medicine, Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
Nat Commun. 2017 Jun 5;8:15533. doi: 10.1038/ncomms15533.
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 of BRAF (22/32) is only detected in PTC, while mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusive SPOP, EZH1 and ZNF148 mutations 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.
良性甲状腺结节（尤其是最常见的增生性病变之一——腺瘤样结节）的基因组改变研究甚少。在这里，我们展示了伴有或不伴有偶然甲状腺乳头状癌（PTC）的腺瘤样结节的全外显子组测序和/或转录组测序数据。BRAF 体细胞突变（22/32）仅在 PTC 中检测到，而 SPOP（4/38）、ZNF148（6/38）和 EZH1（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，相互排斥的 SPOP、EZH1 和 ZNF148 突变在其中的 24.3%中被鉴定出来。腺瘤样结节与偶然的 PTC 相比，具有很少重叠的突变和独特的基因表达模式。系统发育树分析揭示了 PTC 与其匹配的良性结节是独立进化的。我们的研究结果表明，良性结节具有独特的分子特征，与 PTC 不同，并为 PTC 和良性结节具有独立起源的传统观点提供了基因组证据。
