Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
Copyright © 2021 Luo, Liao, Qin, Hou, Xue, Liu, Shen, Wang, Jiang, Song, Chen, Zhang, Wei, Dai, Yang, Zhang, Li, Xu, Zhu and Shu..
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 , TP53R342*) 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Frontiers in oncology - 11(2021) vom: 03., Seite 620924 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Luo, Han [VerfasserIn] |
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| Links: |
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| Themen: |
Brain metastasis |
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| Anmerkungen: |
Date Revised 07.11.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2021.620924 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM327955023 |
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| 520 | |a Copyright © 2021 Luo, Liao, Qin, Hou, Xue, Liu, Shen, Wang, Jiang, Song, Chen, Zhang, Wei, Dai, Yang, Zhang, Li, Xu, Zhu and Shu. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 , TP53R342*) 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 | ||
| 520 | |a CONCLUSION: Genomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Hou, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Zhinan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Feiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuelan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Linlin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Haining |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lingyun |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Lunzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhihui |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jingqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Yang |e verfasserin |4 aut | |
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