- Thyroid
- Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis
-
Mijin Kim, Chae Hwa Kwon, Min Hee Jang, Jeong Mi Kim, Eun Heui Kim, Yun Kyung Jeon, Sang Soo Kim, Kyung-Un Choi, In Joo Kim, Meeyoung Park, Bo Hyun Kim
-
Endocrinol Metab. 2021;36(5):1086-1094. Published online October 28, 2021
-
DOI: https://doi.org/10.3803/EnM.2021.1132
-
-
4,280
View
-
115
Download
-
5
Web of Science
-
4
Crossref
-
 Abstract
 PDF Supplementary Material PubReader  ePub
- Background
Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC.
Methods
Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues.
Results
The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher’s exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs.
Conclusion
This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.
-
Citations
Citations to this article as recorded by  - What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?
Bobby White, Pawel Swietach
Pflügers Archiv - European Journal of Physiology.2024; 476(4): 673. CrossRef - Comprehensive Long-Read Sequencing Analysis Discloses the Transcriptome Features of Papillary Thyroid Microcarcinoma
Yanqiang Wang, Binbin Zou, Yanyan Zhang, Jin Zhang, Shujing Li, Bo Yu, Zhekun An, Lei Li, Siqian Cui, Yutong Zhang, Jiali Yao, Xiuzhi Shi, Jing Liu
The Journal of Clinical Endocrinology & Metabolism.2024; 109(5): 1263. CrossRef - Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations
Liyuan Ma, Luying Gao, Ya Hu, Xiaoyi Li, Chunhao Liu, Jiang Ji, Xinlong Shi, Aonan Pan, Yuang An, Nengwen Luo, Yu Xia, Yuxin Jiang
Clinical Genetics.2024; 105(5): 567. CrossRef - Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
Dan-ni He, Na Wang, Xiao-Ling Wen, Xu-Hua Li, Yu Guo, Shu-heng Fu, Fei-fan Xiong, Zhe-yu Wu, Xu Zhu, Xiao-ling Gao, Zhen-zhen Wang, Hong-jiu Wang
Frontiers in Genetics.2023;[Epub] CrossRef
|
KES
