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Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
BACKGROUND: Brain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC. METHOD: Chronologically resected specimen...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260944/ https://www.ncbi.nlm.nih.gov/pubmed/34249677 http://dx.doi.org/10.3389/fonc.2021.620924 |
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author | Luo, Han Liao, Xue Qin, Yun Hou, Qianqian Xue, Zhinan Liu, Yang Shen, Feiyang Wang, Yuelan Jiang, Yong Song, Linlin Chen, Haining Zhang, Lingyun Wei, Tao Dai, Lunzhi Yang, Li Zhang, Wei Li, Zhihui Xu, Heng Zhu, Jingqiang Shu, Yang |
author_facet | Luo, Han Liao, Xue Qin, Yun Hou, Qianqian Xue, Zhinan Liu, Yang Shen, Feiyang Wang, Yuelan Jiang, Yong Song, Linlin Chen, Haining Zhang, Lingyun Wei, Tao Dai, Lunzhi Yang, Li Zhang, Wei Li, Zhihui Xu, Heng Zhu, Jingqiang Shu, Yang |
author_sort | Luo, Han |
collection | PubMed |
description | BACKGROUND: Brain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC. METHOD: Chronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations. RESULTS: Contrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4(R24C), TP53(R342*)) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4(R24C) introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability. CONCLUSION: Genomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. |
format | Online Article Text |
id | pubmed-8260944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82609442021-07-08 Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis Luo, Han Liao, Xue Qin, Yun Hou, Qianqian Xue, Zhinan Liu, Yang Shen, Feiyang Wang, Yuelan Jiang, Yong Song, Linlin Chen, Haining Zhang, Lingyun Wei, Tao Dai, Lunzhi Yang, Li Zhang, Wei Li, Zhihui Xu, Heng Zhu, Jingqiang Shu, Yang Front Oncol Oncology BACKGROUND: Brain metastasis is extremely rare but predicts dismal prognosis in papillary thyroid cancer (PTC). Dynamic evaluation of stepwise metastatic lesions was barely conducted to identify the longitudinal genomic evolution of brain metastasis in PTC. METHOD: Chronologically resected specimen was analyzed by whole exome sequencing, including four metastatic lymph nodes (lyn 1–4) and brain metastasis lesion (BM). Phylogenetic tree was reconstructed to infer the metastatic pattern and the potential functional mutations. RESULTS: Contrasting with lyn1, ipsilateral metastatic lesions (lyn2–4 and BM) with shared biallelic mutations of TSC2 indicated different genetic originations from multifocal tumors. Lyn 3/4, particularly lyn4 exhibited high genetic similarity with BM. Besides the similar mutational compositions and signatures, shared functional mutations (CDK4(R24C), TP53(R342*)) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4(R24C) introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability. CONCLUSION: Genomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. Frontiers Media S.A. 2021-06-23 /pmc/articles/PMC8260944/ /pubmed/34249677 http://dx.doi.org/10.3389/fonc.2021.620924 Text en Copyright © 2021 Luo, Liao, Qin, Hou, Xue, Liu, Shen, Wang, Jiang, Song, Chen, Zhang, Wei, Dai, Yang, Zhang, Li, Xu, Zhu and Shu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Luo, Han Liao, Xue Qin, Yun Hou, Qianqian Xue, Zhinan Liu, Yang Shen, Feiyang Wang, Yuelan Jiang, Yong Song, Linlin Chen, Haining Zhang, Lingyun Wei, Tao Dai, Lunzhi Yang, Li Zhang, Wei Li, Zhihui Xu, Heng Zhu, Jingqiang Shu, Yang Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis |
title | Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis |
title_full | Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis |
title_fullStr | Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis |
title_full_unstemmed | Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis |
title_short | Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis |
title_sort | longitudinal genomic evolution of conventional papillary thyroid cancer with brain metastasis |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260944/ https://www.ncbi.nlm.nih.gov/pubmed/34249677 http://dx.doi.org/10.3389/fonc.2021.620924 |
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