Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer
Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2021-04, Vol.106 (4), p.e988-e998 |
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| creator | Zhang, Lingyun Ren, Zhixiang Su, Zhengzheng Liu, Yang Yang, Tian Cao, Minyuan Jiang, Yong Tang, Ying Chen, Haining Zhang, Weihan Gong, Rixiang Wei, Tao Peng, Yong Liu, Bo Zhang, Wei Yang, Li Hu, Yiguo Li, Zhihui Zhu, Jingqiang Xu, Heng Shu, Yang Luo, Han |
| description | Abstract
Background
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients.
Methods
Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated.
Results
The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways.
Conclusions
This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis. |
| doi_str_mv | 10.1210/clinem/dgab014 |
| format | Article |
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Background
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients.
Methods
Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated.
Results
The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways.
Conclusions
This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgab014</identifier><identifier>PMID: 33428730</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Analysis ; Cancer ; Cancer patients ; Copy number ; Gene mutations ; Genes ; Genetic aspects ; Genomics ; Kinases ; Malignancy ; Mutation ; p53 Protein ; Patients ; Rapamycin ; Thyroid cancer ; TOR protein ; Tumor proteins ; Tumorigenesis ; Wnt protein</subject><ispartof>The journal of clinical endocrinology and metabolism, 2021-04, Vol.106 (4), p.e988-e998</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-d1a3219887c399d67551150012509ce4e9d4430cd17b7d0ff7d0b0574634ef333</citedby><cites>FETCH-LOGICAL-c464t-d1a3219887c399d67551150012509ce4e9d4430cd17b7d0ff7d0b0574634ef333</cites><orcidid>0000-0002-7748-2621</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33428730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Lingyun</creatorcontrib><creatorcontrib>Ren, Zhixiang</creatorcontrib><creatorcontrib>Su, Zhengzheng</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Yang, Tian</creatorcontrib><creatorcontrib>Cao, Minyuan</creatorcontrib><creatorcontrib>Jiang, Yong</creatorcontrib><creatorcontrib>Tang, Ying</creatorcontrib><creatorcontrib>Chen, Haining</creatorcontrib><creatorcontrib>Zhang, Weihan</creatorcontrib><creatorcontrib>Gong, Rixiang</creatorcontrib><creatorcontrib>Wei, Tao</creatorcontrib><creatorcontrib>Peng, Yong</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Hu, Yiguo</creatorcontrib><creatorcontrib>Li, Zhihui</creatorcontrib><creatorcontrib>Zhu, Jingqiang</creatorcontrib><creatorcontrib>Xu, Heng</creatorcontrib><creatorcontrib>Shu, Yang</creatorcontrib><creatorcontrib>Luo, Han</creatorcontrib><title>Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Background
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients.
Methods
Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated.
Results
The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways.
Conclusions
This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Copy number</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Kinases</subject><subject>Malignancy</subject><subject>Mutation</subject><subject>p53 Protein</subject><subject>Patients</subject><subject>Rapamycin</subject><subject>Thyroid cancer</subject><subject>TOR protein</subject><subject>Tumor proteins</subject><subject>Tumorigenesis</subject><subject>Wnt protein</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkd9rFDEQx4NY7LX66qMEfNGHbfNzs3k8Dm2FUou01LeQS2Z7KbvJmewK_e9NudNCKcjADAyf-c4Xvgi9p-SEMkpO3RAijKf-zq4JFa_QgmohG0W1eo0WhDDaaMV-HqKjUu5JJYTkb9Ah54J1ipMFurpMv2HAP8DNOUOc8HKYIIPHZxCh4BDxalM_FMBXdgoVKPg2TBu8jHY72DIFh683DzkFj1c2Oshv0UFvhwLv9vMY3Xz9cr06by6-n31bLS8aJ1oxNZ5azqjuOuW41r5VUlIqq0MmiXYgQHshOHGeqrXypO9rWxOpRMsF9JzzY_Rpp7vN6dcMZTJjKA6GwUZIczFMKMWkJl1X0Y_P0Ps051jdGaZlSzkllDxRd3YAE2Kfpmzdo6hZKsIEk7JVlTp5garlYQwuRehD3b904HIqJUNvtjmMNj8YSsxjhGYXodlHWA8-7N3O6xH8P_xvZhX4vAPSvP2f2B_IFaNb</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Zhang, Lingyun</creator><creator>Ren, Zhixiang</creator><creator>Su, Zhengzheng</creator><creator>Liu, Yang</creator><creator>Yang, Tian</creator><creator>Cao, Minyuan</creator><creator>Jiang, Yong</creator><creator>Tang, Ying</creator><creator>Chen, Haining</creator><creator>Zhang, Weihan</creator><creator>Gong, Rixiang</creator><creator>Wei, Tao</creator><creator>Peng, Yong</creator><creator>Liu, Bo</creator><creator>Zhang, Wei</creator><creator>Yang, Li</creator><creator>Hu, Yiguo</creator><creator>Li, Zhihui</creator><creator>Zhu, Jingqiang</creator><creator>Xu, Heng</creator><creator>Shu, Yang</creator><creator>Luo, Han</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7748-2621</orcidid></search><sort><creationdate>20210401</creationdate><title>Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer</title><author>Zhang, Lingyun ; Ren, Zhixiang ; Su, Zhengzheng ; Liu, Yang ; Yang, Tian ; Cao, Minyuan ; Jiang, Yong ; Tang, Ying ; Chen, Haining ; Zhang, Weihan ; Gong, Rixiang ; Wei, Tao ; Peng, Yong ; Liu, Bo ; Zhang, Wei ; Yang, Li ; Hu, Yiguo ; Li, Zhihui ; Zhu, Jingqiang ; Xu, Heng ; Shu, Yang ; Luo, Han</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-d1a3219887c399d67551150012509ce4e9d4430cd17b7d0ff7d0b0574634ef333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Copy number</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomics</topic><topic>Kinases</topic><topic>Malignancy</topic><topic>Mutation</topic><topic>p53 Protein</topic><topic>Patients</topic><topic>Rapamycin</topic><topic>Thyroid cancer</topic><topic>TOR protein</topic><topic>Tumor proteins</topic><topic>Tumorigenesis</topic><topic>Wnt protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Lingyun</creatorcontrib><creatorcontrib>Ren, Zhixiang</creatorcontrib><creatorcontrib>Su, Zhengzheng</creatorcontrib><creatorcontrib>Liu, Yang</creatorcontrib><creatorcontrib>Yang, Tian</creatorcontrib><creatorcontrib>Cao, Minyuan</creatorcontrib><creatorcontrib>Jiang, Yong</creatorcontrib><creatorcontrib>Tang, Ying</creatorcontrib><creatorcontrib>Chen, Haining</creatorcontrib><creatorcontrib>Zhang, Weihan</creatorcontrib><creatorcontrib>Gong, Rixiang</creatorcontrib><creatorcontrib>Wei, Tao</creatorcontrib><creatorcontrib>Peng, Yong</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Yang, Li</creatorcontrib><creatorcontrib>Hu, Yiguo</creatorcontrib><creatorcontrib>Li, Zhihui</creatorcontrib><creatorcontrib>Zhu, Jingqiang</creatorcontrib><creatorcontrib>Xu, Heng</creatorcontrib><creatorcontrib>Shu, Yang</creatorcontrib><creatorcontrib>Luo, Han</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Lingyun</au><au>Ren, Zhixiang</au><au>Su, Zhengzheng</au><au>Liu, Yang</au><au>Yang, Tian</au><au>Cao, Minyuan</au><au>Jiang, Yong</au><au>Tang, Ying</au><au>Chen, Haining</au><au>Zhang, Weihan</au><au>Gong, Rixiang</au><au>Wei, Tao</au><au>Peng, Yong</au><au>Liu, Bo</au><au>Zhang, Wei</au><au>Yang, Li</au><au>Hu, Yiguo</au><au>Li, Zhihui</au><au>Zhu, Jingqiang</au><au>Xu, Heng</au><au>Shu, Yang</au><au>Luo, Han</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>106</volume><issue>4</issue><spage>e988</spage><epage>e998</epage><pages>e988-e998</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Background
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients.
Methods
Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated.
Results
The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways.
Conclusions
This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33428730</pmid><doi>10.1210/clinem/dgab014</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7748-2621</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Analysis Cancer Cancer patients Copy number Gene mutations Genes Genetic aspects Genomics Kinases Malignancy Mutation p53 Protein Patients Rapamycin Thyroid cancer TOR protein Tumor proteins Tumorigenesis Wnt protein |
| title | Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer |
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