Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis

BackgroundBrain 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.MethodChronologically resected specimen was a...
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Autor*in:	Han Luo [verfasserIn] Xue Liao [verfasserIn] Yun Qin [verfasserIn] Qianqian Hou [verfasserIn] Zhinan Xue [verfasserIn] Yang Liu [verfasserIn] Feiyang Shen [verfasserIn] Yuelan Wang [verfasserIn] Yong Jiang [verfasserIn] Linlin Song [verfasserIn] Haining Chen [verfasserIn] Lingyun Zhang [verfasserIn] Tao Wei [verfasserIn] Lunzhi Dai [verfasserIn] Li Yang [verfasserIn] Wei Zhang [verfasserIn] Zhihui Li [verfasserIn] Heng Xu [verfasserIn] Jingqiang Zhu [verfasserIn] Yang Shu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	brain metastasis thyroid cancer cancer evolution genetics CDK4

Übergeordnetes Werk:	In: Frontiers in Oncology - Frontiers Media S.A., 2012, 11(2021)
Übergeordnetes Werk:	volume:11 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fonc.2021.620924

Katalog-ID:	DOAJ072253940

Internformat


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245	1	0	\|a Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
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520			\|a BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.
650		4	\|a brain metastasis
650		4	\|a thyroid cancer
650		4	\|a cancer evolution
650		4	\|a genetics
650		4	\|a CDK4
653		0	\|a Neoplasms. Tumors. Oncology. Including cancer and carcinogens
700	0		\|a Xue Liao \|e verfasserin \|4 aut
700	0		\|a Yun Qin \|e verfasserin \|4 aut
700	0		\|a Qianqian Hou \|e verfasserin \|4 aut
700	0		\|a Zhinan Xue \|e verfasserin \|4 aut
700	0		\|a Yang Liu \|e verfasserin \|4 aut
700	0		\|a Yang Liu \|e verfasserin \|4 aut
700	0		\|a Feiyang Shen \|e verfasserin \|4 aut
700	0		\|a Yuelan Wang \|e verfasserin \|4 aut
700	0		\|a Yong Jiang \|e verfasserin \|4 aut
700	0		\|a Linlin Song \|e verfasserin \|4 aut
700	0		\|a Linlin Song \|e verfasserin \|4 aut
700	0		\|a Haining Chen \|e verfasserin \|4 aut
700	0		\|a Lingyun Zhang \|e verfasserin \|4 aut
700	0		\|a Lingyun Zhang \|e verfasserin \|4 aut
700	0		\|a Tao Wei \|e verfasserin \|4 aut
700	0		\|a Lunzhi Dai \|e verfasserin \|4 aut
700	0		\|a Li Yang \|e verfasserin \|4 aut
700	0		\|a Wei Zhang \|e verfasserin \|4 aut
700	0		\|a Zhihui Li \|e verfasserin \|4 aut
700	0		\|a Heng Xu \|e verfasserin \|4 aut
700	0		\|a Heng Xu \|e verfasserin \|4 aut
700	0		\|a Jingqiang Zhu \|e verfasserin \|4 aut
700	0		\|a Yang Shu \|e verfasserin \|4 aut
700	0		\|a Yang Shu \|e verfasserin \|4 aut
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allfields	10.3389/fonc.2021.620924 doi (DE-627)DOAJ072253940 (DE-599)DOAJ4d8974ba9fa34966be22dc9eec5ce9ca DE-627 ger DE-627 rakwb eng RC254-282 Han Luo verfasserin aut Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. brain metastasis thyroid cancer cancer evolution genetics CDK4 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xue Liao verfasserin aut Yun Qin verfasserin aut Qianqian Hou verfasserin aut Zhinan Xue verfasserin aut Yang Liu verfasserin aut Yang Liu verfasserin aut Feiyang Shen verfasserin aut Yuelan Wang verfasserin aut Yong Jiang verfasserin aut Linlin Song verfasserin aut Linlin Song verfasserin aut Haining Chen verfasserin aut Lingyun Zhang verfasserin aut Lingyun Zhang verfasserin aut Tao Wei verfasserin aut Lunzhi Dai verfasserin aut Li Yang verfasserin aut Wei Zhang verfasserin aut Zhihui Li verfasserin aut Heng Xu verfasserin aut Heng Xu verfasserin aut Jingqiang Zhu verfasserin aut Yang Shu verfasserin aut Yang Shu verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 11(2021) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:11 year:2021 https://doi.org/10.3389/fonc.2021.620924 kostenfrei https://doaj.org/article/4d8974ba9fa34966be22dc9eec5ce9ca kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2021.620924/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
spelling	10.3389/fonc.2021.620924 doi (DE-627)DOAJ072253940 (DE-599)DOAJ4d8974ba9fa34966be22dc9eec5ce9ca DE-627 ger DE-627 rakwb eng RC254-282 Han Luo verfasserin aut Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. brain metastasis thyroid cancer cancer evolution genetics CDK4 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xue Liao verfasserin aut Yun Qin verfasserin aut Qianqian Hou verfasserin aut Zhinan Xue verfasserin aut Yang Liu verfasserin aut Yang Liu verfasserin aut Feiyang Shen verfasserin aut Yuelan Wang verfasserin aut Yong Jiang verfasserin aut Linlin Song verfasserin aut Linlin Song verfasserin aut Haining Chen verfasserin aut Lingyun Zhang verfasserin aut Lingyun Zhang verfasserin aut Tao Wei verfasserin aut Lunzhi Dai verfasserin aut Li Yang verfasserin aut Wei Zhang verfasserin aut Zhihui Li verfasserin aut Heng Xu verfasserin aut Heng Xu verfasserin aut Jingqiang Zhu verfasserin aut Yang Shu verfasserin aut Yang Shu verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 11(2021) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:11 year:2021 https://doi.org/10.3389/fonc.2021.620924 kostenfrei https://doaj.org/article/4d8974ba9fa34966be22dc9eec5ce9ca kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2021.620924/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
allfields_unstemmed	10.3389/fonc.2021.620924 doi (DE-627)DOAJ072253940 (DE-599)DOAJ4d8974ba9fa34966be22dc9eec5ce9ca DE-627 ger DE-627 rakwb eng RC254-282 Han Luo verfasserin aut Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. brain metastasis thyroid cancer cancer evolution genetics CDK4 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xue Liao verfasserin aut Yun Qin verfasserin aut Qianqian Hou verfasserin aut Zhinan Xue verfasserin aut Yang Liu verfasserin aut Yang Liu verfasserin aut Feiyang Shen verfasserin aut Yuelan Wang verfasserin aut Yong Jiang verfasserin aut Linlin Song verfasserin aut Linlin Song verfasserin aut Haining Chen verfasserin aut Lingyun Zhang verfasserin aut Lingyun Zhang verfasserin aut Tao Wei verfasserin aut Lunzhi Dai verfasserin aut Li Yang verfasserin aut Wei Zhang verfasserin aut Zhihui Li verfasserin aut Heng Xu verfasserin aut Heng Xu verfasserin aut Jingqiang Zhu verfasserin aut Yang Shu verfasserin aut Yang Shu verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 11(2021) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:11 year:2021 https://doi.org/10.3389/fonc.2021.620924 kostenfrei https://doaj.org/article/4d8974ba9fa34966be22dc9eec5ce9ca kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2021.620924/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
allfieldsGer	10.3389/fonc.2021.620924 doi (DE-627)DOAJ072253940 (DE-599)DOAJ4d8974ba9fa34966be22dc9eec5ce9ca DE-627 ger DE-627 rakwb eng RC254-282 Han Luo verfasserin aut Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. brain metastasis thyroid cancer cancer evolution genetics CDK4 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xue Liao verfasserin aut Yun Qin verfasserin aut Qianqian Hou verfasserin aut Zhinan Xue verfasserin aut Yang Liu verfasserin aut Yang Liu verfasserin aut Feiyang Shen verfasserin aut Yuelan Wang verfasserin aut Yong Jiang verfasserin aut Linlin Song verfasserin aut Linlin Song verfasserin aut Haining Chen verfasserin aut Lingyun Zhang verfasserin aut Lingyun Zhang verfasserin aut Tao Wei verfasserin aut Lunzhi Dai verfasserin aut Li Yang verfasserin aut Wei Zhang verfasserin aut Zhihui Li verfasserin aut Heng Xu verfasserin aut Heng Xu verfasserin aut Jingqiang Zhu verfasserin aut Yang Shu verfasserin aut Yang Shu verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 11(2021) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:11 year:2021 https://doi.org/10.3389/fonc.2021.620924 kostenfrei https://doaj.org/article/4d8974ba9fa34966be22dc9eec5ce9ca kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2021.620924/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
allfieldsSound	10.3389/fonc.2021.620924 doi (DE-627)DOAJ072253940 (DE-599)DOAJ4d8974ba9fa34966be22dc9eec5ce9ca DE-627 ger DE-627 rakwb eng RC254-282 Han Luo verfasserin aut Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC. brain metastasis thyroid cancer cancer evolution genetics CDK4 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xue Liao verfasserin aut Yun Qin verfasserin aut Qianqian Hou verfasserin aut Zhinan Xue verfasserin aut Yang Liu verfasserin aut Yang Liu verfasserin aut Feiyang Shen verfasserin aut Yuelan Wang verfasserin aut Yong Jiang verfasserin aut Linlin Song verfasserin aut Linlin Song verfasserin aut Haining Chen verfasserin aut Lingyun Zhang verfasserin aut Lingyun Zhang verfasserin aut Tao Wei verfasserin aut Lunzhi Dai verfasserin aut Li Yang verfasserin aut Wei Zhang verfasserin aut Zhihui Li verfasserin aut Heng Xu verfasserin aut Heng Xu verfasserin aut Jingqiang Zhu verfasserin aut Yang Shu verfasserin aut Yang Shu verfasserin aut In Frontiers in Oncology Frontiers Media S.A., 2012 11(2021) (DE-627)684965518 (DE-600)2649216-7 2234943X nnns volume:11 year:2021 https://doi.org/10.3389/fonc.2021.620924 kostenfrei https://doaj.org/article/4d8974ba9fa34966be22dc9eec5ce9ca kostenfrei https://www.frontiersin.org/articles/10.3389/fonc.2021.620924/full kostenfrei https://doaj.org/toc/2234-943X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
language	English
source	In Frontiers in Oncology 11(2021) volume:11 year:2021
sourceStr	In Frontiers in Oncology 11(2021) volume:11 year:2021
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	brain metastasis thyroid cancer cancer evolution genetics CDK4 Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Frontiers in Oncology
authorswithroles_txt_mv	Han Luo @@aut@@ Xue Liao @@aut@@ Yun Qin @@aut@@ Qianqian Hou @@aut@@ Zhinan Xue @@aut@@ Yang Liu @@aut@@ Feiyang Shen @@aut@@ Yuelan Wang @@aut@@ Yong Jiang @@aut@@ Linlin Song @@aut@@ Haining Chen @@aut@@ Lingyun Zhang @@aut@@ Tao Wei @@aut@@ Lunzhi Dai @@aut@@ Li Yang @@aut@@ Wei Zhang @@aut@@ Zhihui Li @@aut@@ Heng Xu @@aut@@ Jingqiang Zhu @@aut@@ Yang Shu @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	684965518
id	DOAJ072253940
language_de	englisch
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callnumber-first	R - Medicine
author	Han Luo
spellingShingle	Han Luo misc RC254-282 misc brain metastasis misc thyroid cancer misc cancer evolution misc genetics misc CDK4 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
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topic_title	RC254-282 Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis brain metastasis thyroid cancer cancer evolution genetics CDK4
topic	misc RC254-282 misc brain metastasis misc thyroid cancer misc cancer evolution misc genetics misc CDK4 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc brain metastasis misc thyroid cancer misc cancer evolution misc genetics misc CDK4 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc brain metastasis misc thyroid cancer misc cancer evolution misc genetics misc CDK4 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
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title_full	Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
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author_browse	Han Luo Xue Liao Yun Qin Qianqian Hou Zhinan Xue Yang Liu Feiyang Shen Yuelan Wang Yong Jiang Linlin Song Haining Chen Lingyun Zhang Tao Wei Lunzhi Dai Li Yang Wei Zhang Zhihui Li Heng Xu Jingqiang Zhu Yang Shu
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author2-role	verfasserin
title_sort	longitudinal genomic evolution of conventional papillary thyroid cancer with brain metastasis
callnumber	RC254-282
title_auth	Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
abstract	BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.
abstractGer	BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.
abstract_unstemmed	BackgroundBrain 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.MethodChronologically 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.ResultsContrasting 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 (CDK4R24C, TP53R342*) were observed in lyn3/4 and BM. Frequencies of these mutations gradually increase along with the metastasis progression. Consistently, TP53 knockout and CDK4R24C introduction in PTC cells significantly decreased radioiodine uptake and increased metastatic ability.ConclusionGenomic mutations in CDK4 and TP53 during the tumor evolution may contribute to the lymph node and brain metastasis of PTC.
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title_short	Longitudinal Genomic Evolution of Conventional Papillary Thyroid Cancer With Brain Metastasis
url	https://doi.org/10.3389/fonc.2021.620924 https://doaj.org/article/4d8974ba9fa34966be22dc9eec5ce9ca https://www.frontiersin.org/articles/10.3389/fonc.2021.620924/full https://doaj.org/toc/2234-943X
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author2	Xue Liao Yun Qin Qianqian Hou Zhinan Xue Yang Liu Feiyang Shen Yuelan Wang Yong Jiang Linlin Song Haining Chen Lingyun Zhang Tao Wei Lunzhi Dai Li Yang Wei Zhang Zhihui Li Heng Xu Jingqiang Zhu Yang Shu
author2Str	Xue Liao Yun Qin Qianqian Hou Zhinan Xue Yang Liu Feiyang Shen Yuelan Wang Yong Jiang Linlin Song Haining Chen Lingyun Zhang Tao Wei Lunzhi Dai Li Yang Wei Zhang Zhihui Li Heng Xu Jingqiang Zhu Yang Shu
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up_date	2024-07-04T00:21:07.066Z
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