Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are...
Gespeichert in:
| Veröffentlicht in: | Genome research 2013-09, Vol.23 (9), p.1422-1433 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1433 |
|---|---|
| container_issue | 9 |
| container_start_page | 1422 |
| container_title | Genome research |
| container_volume | 23 |
| creator | Kan, Zhengyan Zheng, Hancheng Liu, Xiao Li, Shuyu Barber, Thomas D Gong, Zhuolin Gao, Huan Hao, Ke Willard, Melinda D Xu, Jiangchun Hauptschein, Robert Rejto, Paul A Fernandez, Julio Wang, Guan Zhang, Qinghui Wang, Bo Chen, Ronghua Wang, Jian Lee, Nikki P Zhou, Wei Lin, Zhao Peng, Zhiyu Yi, Kang Chen, Shengpei Li, Lin Fan, Xiaomei Yang, Jie Ye, Rui Ju, Jia Wang, Kai Estrella, Heather Deng, Shibing Wei, Ping Qiu, Ming Wulur, Isabella H Liu, Jiangang Ehsani, Mariam E Zhang, Chunsheng Loboda, Andrey Sung, Wing Kin Aggarwal, Amit Poon, Ronnie T Fan, Sheung Tat Wang, Jun Hardwick, James Reinhard, Christoph Dai, Hongyue Li, Yingrui Luk, John M Mao, Mao |
| description | Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease. |
| doi_str_mv | 10.1101/gr.154492.113 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3759719</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1429642666</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-8b4ea4e8c71b25cdfd5d74bc25057aa683fc5cf27a38c994560ccd0a096ef24c3</originalsourceid><addsrcrecordid>eNqNUU1LxDAUDKK4fh29So9eqvluchFE_AJBEMVjyKav3UjbrEkr-O_NsrrozdN7w5s3zDAIHRN8Rggm5208I4JzTTNkW2gvA10KLvV23rFSpcaCzNB-Sm8YY8aV2kUzyiqlpKB76Ol1ETooWxhCD0WC9wkG54e28DUMo288pCKCm2LMsOin0Y4-DKnwQ7GApR2Dg66bOhsLZ2N-DL09RDuN7RIcfc8D9HJz_Xx1Vz483t5fXT6Ujis5lmrOwXJQriJzKlzd1KKu-NxRgUVlrVSsccI1tLJMOa25kNi5GlusJTSUO3aALta6y2neQ-2ywWg7s4y-t_HTBOvN38vgF6YNH4ZVQldEZ4HTb4EYcu40mt6nVR47QJiSIZxpSpSk7B9UqiWnUspMLddUF0NKEZqNI4LNqjLTRrOuLMOV9MnvGBv2T0fsC63DlL8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1429642666</pqid></control><display><type>article</type><title>Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Kan, Zhengyan ; Zheng, Hancheng ; Liu, Xiao ; Li, Shuyu ; Barber, Thomas D ; Gong, Zhuolin ; Gao, Huan ; Hao, Ke ; Willard, Melinda D ; Xu, Jiangchun ; Hauptschein, Robert ; Rejto, Paul A ; Fernandez, Julio ; Wang, Guan ; Zhang, Qinghui ; Wang, Bo ; Chen, Ronghua ; Wang, Jian ; Lee, Nikki P ; Zhou, Wei ; Lin, Zhao ; Peng, Zhiyu ; Yi, Kang ; Chen, Shengpei ; Li, Lin ; Fan, Xiaomei ; Yang, Jie ; Ye, Rui ; Ju, Jia ; Wang, Kai ; Estrella, Heather ; Deng, Shibing ; Wei, Ping ; Qiu, Ming ; Wulur, Isabella H ; Liu, Jiangang ; Ehsani, Mariam E ; Zhang, Chunsheng ; Loboda, Andrey ; Sung, Wing Kin ; Aggarwal, Amit ; Poon, Ronnie T ; Fan, Sheung Tat ; Wang, Jun ; Hardwick, James ; Reinhard, Christoph ; Dai, Hongyue ; Li, Yingrui ; Luk, John M ; Mao, Mao</creator><creatorcontrib>Kan, Zhengyan ; Zheng, Hancheng ; Liu, Xiao ; Li, Shuyu ; Barber, Thomas D ; Gong, Zhuolin ; Gao, Huan ; Hao, Ke ; Willard, Melinda D ; Xu, Jiangchun ; Hauptschein, Robert ; Rejto, Paul A ; Fernandez, Julio ; Wang, Guan ; Zhang, Qinghui ; Wang, Bo ; Chen, Ronghua ; Wang, Jian ; Lee, Nikki P ; Zhou, Wei ; Lin, Zhao ; Peng, Zhiyu ; Yi, Kang ; Chen, Shengpei ; Li, Lin ; Fan, Xiaomei ; Yang, Jie ; Ye, Rui ; Ju, Jia ; Wang, Kai ; Estrella, Heather ; Deng, Shibing ; Wei, Ping ; Qiu, Ming ; Wulur, Isabella H ; Liu, Jiangang ; Ehsani, Mariam E ; Zhang, Chunsheng ; Loboda, Andrey ; Sung, Wing Kin ; Aggarwal, Amit ; Poon, Ronnie T ; Fan, Sheung Tat ; Wang, Jun ; Hardwick, James ; Reinhard, Christoph ; Dai, Hongyue ; Li, Yingrui ; Luk, John M ; Mao, Mao</creatorcontrib><description>Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.</description><identifier>ISSN: 1088-9051</identifier><identifier>EISSN: 1549-5469</identifier><identifier>DOI: 10.1101/gr.154492.113</identifier><identifier>PMID: 23788652</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>Amino Acid Sequence ; beta Catenin - genetics ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - virology ; DNA, Viral - genetics ; Female ; Genome, Human ; Hepatitis B virus ; Hepatitis B virus - genetics ; Humans ; Janus Kinase 1 - genetics ; Liver Neoplasms - genetics ; Liver Neoplasms - virology ; Male ; Molecular Sequence Data ; Mutation ; Sequence Analysis, DNA ; STAT Transcription Factors - genetics ; Tumor Suppressor Protein p53 - genetics ; Virus Integration ; Wnt Signaling Pathway - genetics</subject><ispartof>Genome research, 2013-09, Vol.23 (9), p.1422-1433</ispartof><rights>2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-8b4ea4e8c71b25cdfd5d74bc25057aa683fc5cf27a38c994560ccd0a096ef24c3</citedby><cites>FETCH-LOGICAL-c486t-8b4ea4e8c71b25cdfd5d74bc25057aa683fc5cf27a38c994560ccd0a096ef24c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759719/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759719/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23788652$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kan, Zhengyan</creatorcontrib><creatorcontrib>Zheng, Hancheng</creatorcontrib><creatorcontrib>Liu, Xiao</creatorcontrib><creatorcontrib>Li, Shuyu</creatorcontrib><creatorcontrib>Barber, Thomas D</creatorcontrib><creatorcontrib>Gong, Zhuolin</creatorcontrib><creatorcontrib>Gao, Huan</creatorcontrib><creatorcontrib>Hao, Ke</creatorcontrib><creatorcontrib>Willard, Melinda D</creatorcontrib><creatorcontrib>Xu, Jiangchun</creatorcontrib><creatorcontrib>Hauptschein, Robert</creatorcontrib><creatorcontrib>Rejto, Paul A</creatorcontrib><creatorcontrib>Fernandez, Julio</creatorcontrib><creatorcontrib>Wang, Guan</creatorcontrib><creatorcontrib>Zhang, Qinghui</creatorcontrib><creatorcontrib>Wang, Bo</creatorcontrib><creatorcontrib>Chen, Ronghua</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Lee, Nikki P</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Lin, Zhao</creatorcontrib><creatorcontrib>Peng, Zhiyu</creatorcontrib><creatorcontrib>Yi, Kang</creatorcontrib><creatorcontrib>Chen, Shengpei</creatorcontrib><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Fan, Xiaomei</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Ye, Rui</creatorcontrib><creatorcontrib>Ju, Jia</creatorcontrib><creatorcontrib>Wang, Kai</creatorcontrib><creatorcontrib>Estrella, Heather</creatorcontrib><creatorcontrib>Deng, Shibing</creatorcontrib><creatorcontrib>Wei, Ping</creatorcontrib><creatorcontrib>Qiu, Ming</creatorcontrib><creatorcontrib>Wulur, Isabella H</creatorcontrib><creatorcontrib>Liu, Jiangang</creatorcontrib><creatorcontrib>Ehsani, Mariam E</creatorcontrib><creatorcontrib>Zhang, Chunsheng</creatorcontrib><creatorcontrib>Loboda, Andrey</creatorcontrib><creatorcontrib>Sung, Wing Kin</creatorcontrib><creatorcontrib>Aggarwal, Amit</creatorcontrib><creatorcontrib>Poon, Ronnie T</creatorcontrib><creatorcontrib>Fan, Sheung Tat</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Hardwick, James</creatorcontrib><creatorcontrib>Reinhard, Christoph</creatorcontrib><creatorcontrib>Dai, Hongyue</creatorcontrib><creatorcontrib>Li, Yingrui</creatorcontrib><creatorcontrib>Luk, John M</creatorcontrib><creatorcontrib>Mao, Mao</creatorcontrib><title>Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma</title><title>Genome research</title><addtitle>Genome Res</addtitle><description>Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.</description><subject>Amino Acid Sequence</subject><subject>beta Catenin - genetics</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>DNA, Viral - genetics</subject><subject>Female</subject><subject>Genome, Human</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - genetics</subject><subject>Humans</subject><subject>Janus Kinase 1 - genetics</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - virology</subject><subject>Male</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Sequence Analysis, DNA</subject><subject>STAT Transcription Factors - genetics</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Virus Integration</subject><subject>Wnt Signaling Pathway - genetics</subject><issn>1088-9051</issn><issn>1549-5469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1LxDAUDKK4fh29So9eqvluchFE_AJBEMVjyKav3UjbrEkr-O_NsrrozdN7w5s3zDAIHRN8Rggm5208I4JzTTNkW2gvA10KLvV23rFSpcaCzNB-Sm8YY8aV2kUzyiqlpKB76Ol1ETooWxhCD0WC9wkG54e28DUMo288pCKCm2LMsOin0Y4-DKnwQ7GApR2Dg66bOhsLZ2N-DL09RDuN7RIcfc8D9HJz_Xx1Vz483t5fXT6Ujis5lmrOwXJQriJzKlzd1KKu-NxRgUVlrVSsccI1tLJMOa25kNi5GlusJTSUO3aALta6y2neQ-2ywWg7s4y-t_HTBOvN38vgF6YNH4ZVQldEZ4HTb4EYcu40mt6nVR47QJiSIZxpSpSk7B9UqiWnUspMLddUF0NKEZqNI4LNqjLTRrOuLMOV9MnvGBv2T0fsC63DlL8</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Kan, Zhengyan</creator><creator>Zheng, Hancheng</creator><creator>Liu, Xiao</creator><creator>Li, Shuyu</creator><creator>Barber, Thomas D</creator><creator>Gong, Zhuolin</creator><creator>Gao, Huan</creator><creator>Hao, Ke</creator><creator>Willard, Melinda D</creator><creator>Xu, Jiangchun</creator><creator>Hauptschein, Robert</creator><creator>Rejto, Paul A</creator><creator>Fernandez, Julio</creator><creator>Wang, Guan</creator><creator>Zhang, Qinghui</creator><creator>Wang, Bo</creator><creator>Chen, Ronghua</creator><creator>Wang, Jian</creator><creator>Lee, Nikki P</creator><creator>Zhou, Wei</creator><creator>Lin, Zhao</creator><creator>Peng, Zhiyu</creator><creator>Yi, Kang</creator><creator>Chen, Shengpei</creator><creator>Li, Lin</creator><creator>Fan, Xiaomei</creator><creator>Yang, Jie</creator><creator>Ye, Rui</creator><creator>Ju, Jia</creator><creator>Wang, Kai</creator><creator>Estrella, Heather</creator><creator>Deng, Shibing</creator><creator>Wei, Ping</creator><creator>Qiu, Ming</creator><creator>Wulur, Isabella H</creator><creator>Liu, Jiangang</creator><creator>Ehsani, Mariam E</creator><creator>Zhang, Chunsheng</creator><creator>Loboda, Andrey</creator><creator>Sung, Wing Kin</creator><creator>Aggarwal, Amit</creator><creator>Poon, Ronnie T</creator><creator>Fan, Sheung Tat</creator><creator>Wang, Jun</creator><creator>Hardwick, James</creator><creator>Reinhard, Christoph</creator><creator>Dai, Hongyue</creator><creator>Li, Yingrui</creator><creator>Luk, John M</creator><creator>Mao, Mao</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130901</creationdate><title>Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma</title><author>Kan, Zhengyan ; Zheng, Hancheng ; Liu, Xiao ; Li, Shuyu ; Barber, Thomas D ; Gong, Zhuolin ; Gao, Huan ; Hao, Ke ; Willard, Melinda D ; Xu, Jiangchun ; Hauptschein, Robert ; Rejto, Paul A ; Fernandez, Julio ; Wang, Guan ; Zhang, Qinghui ; Wang, Bo ; Chen, Ronghua ; Wang, Jian ; Lee, Nikki P ; Zhou, Wei ; Lin, Zhao ; Peng, Zhiyu ; Yi, Kang ; Chen, Shengpei ; Li, Lin ; Fan, Xiaomei ; Yang, Jie ; Ye, Rui ; Ju, Jia ; Wang, Kai ; Estrella, Heather ; Deng, Shibing ; Wei, Ping ; Qiu, Ming ; Wulur, Isabella H ; Liu, Jiangang ; Ehsani, Mariam E ; Zhang, Chunsheng ; Loboda, Andrey ; Sung, Wing Kin ; Aggarwal, Amit ; Poon, Ronnie T ; Fan, Sheung Tat ; Wang, Jun ; Hardwick, James ; Reinhard, Christoph ; Dai, Hongyue ; Li, Yingrui ; Luk, John M ; Mao, Mao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-8b4ea4e8c71b25cdfd5d74bc25057aa683fc5cf27a38c994560ccd0a096ef24c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Sequence</topic><topic>beta Catenin - genetics</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>DNA, Viral - genetics</topic><topic>Female</topic><topic>Genome, Human</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - genetics</topic><topic>Humans</topic><topic>Janus Kinase 1 - genetics</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - virology</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Sequence Analysis, DNA</topic><topic>STAT Transcription Factors - genetics</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Virus Integration</topic><topic>Wnt Signaling Pathway - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kan, Zhengyan</creatorcontrib><creatorcontrib>Zheng, Hancheng</creatorcontrib><creatorcontrib>Liu, Xiao</creatorcontrib><creatorcontrib>Li, Shuyu</creatorcontrib><creatorcontrib>Barber, Thomas D</creatorcontrib><creatorcontrib>Gong, Zhuolin</creatorcontrib><creatorcontrib>Gao, Huan</creatorcontrib><creatorcontrib>Hao, Ke</creatorcontrib><creatorcontrib>Willard, Melinda D</creatorcontrib><creatorcontrib>Xu, Jiangchun</creatorcontrib><creatorcontrib>Hauptschein, Robert</creatorcontrib><creatorcontrib>Rejto, Paul A</creatorcontrib><creatorcontrib>Fernandez, Julio</creatorcontrib><creatorcontrib>Wang, Guan</creatorcontrib><creatorcontrib>Zhang, Qinghui</creatorcontrib><creatorcontrib>Wang, Bo</creatorcontrib><creatorcontrib>Chen, Ronghua</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Lee, Nikki P</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Lin, Zhao</creatorcontrib><creatorcontrib>Peng, Zhiyu</creatorcontrib><creatorcontrib>Yi, Kang</creatorcontrib><creatorcontrib>Chen, Shengpei</creatorcontrib><creatorcontrib>Li, Lin</creatorcontrib><creatorcontrib>Fan, Xiaomei</creatorcontrib><creatorcontrib>Yang, Jie</creatorcontrib><creatorcontrib>Ye, Rui</creatorcontrib><creatorcontrib>Ju, Jia</creatorcontrib><creatorcontrib>Wang, Kai</creatorcontrib><creatorcontrib>Estrella, Heather</creatorcontrib><creatorcontrib>Deng, Shibing</creatorcontrib><creatorcontrib>Wei, Ping</creatorcontrib><creatorcontrib>Qiu, Ming</creatorcontrib><creatorcontrib>Wulur, Isabella H</creatorcontrib><creatorcontrib>Liu, Jiangang</creatorcontrib><creatorcontrib>Ehsani, Mariam E</creatorcontrib><creatorcontrib>Zhang, Chunsheng</creatorcontrib><creatorcontrib>Loboda, Andrey</creatorcontrib><creatorcontrib>Sung, Wing Kin</creatorcontrib><creatorcontrib>Aggarwal, Amit</creatorcontrib><creatorcontrib>Poon, Ronnie T</creatorcontrib><creatorcontrib>Fan, Sheung Tat</creatorcontrib><creatorcontrib>Wang, Jun</creatorcontrib><creatorcontrib>Hardwick, James</creatorcontrib><creatorcontrib>Reinhard, Christoph</creatorcontrib><creatorcontrib>Dai, Hongyue</creatorcontrib><creatorcontrib>Li, Yingrui</creatorcontrib><creatorcontrib>Luk, John M</creatorcontrib><creatorcontrib>Mao, Mao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genome research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kan, Zhengyan</au><au>Zheng, Hancheng</au><au>Liu, Xiao</au><au>Li, Shuyu</au><au>Barber, Thomas D</au><au>Gong, Zhuolin</au><au>Gao, Huan</au><au>Hao, Ke</au><au>Willard, Melinda D</au><au>Xu, Jiangchun</au><au>Hauptschein, Robert</au><au>Rejto, Paul A</au><au>Fernandez, Julio</au><au>Wang, Guan</au><au>Zhang, Qinghui</au><au>Wang, Bo</au><au>Chen, Ronghua</au><au>Wang, Jian</au><au>Lee, Nikki P</au><au>Zhou, Wei</au><au>Lin, Zhao</au><au>Peng, Zhiyu</au><au>Yi, Kang</au><au>Chen, Shengpei</au><au>Li, Lin</au><au>Fan, Xiaomei</au><au>Yang, Jie</au><au>Ye, Rui</au><au>Ju, Jia</au><au>Wang, Kai</au><au>Estrella, Heather</au><au>Deng, Shibing</au><au>Wei, Ping</au><au>Qiu, Ming</au><au>Wulur, Isabella H</au><au>Liu, Jiangang</au><au>Ehsani, Mariam E</au><au>Zhang, Chunsheng</au><au>Loboda, Andrey</au><au>Sung, Wing Kin</au><au>Aggarwal, Amit</au><au>Poon, Ronnie T</au><au>Fan, Sheung Tat</au><au>Wang, Jun</au><au>Hardwick, James</au><au>Reinhard, Christoph</au><au>Dai, Hongyue</au><au>Li, Yingrui</au><au>Luk, John M</au><au>Mao, Mao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma</atitle><jtitle>Genome research</jtitle><addtitle>Genome Res</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>23</volume><issue>9</issue><spage>1422</spage><epage>1433</epage><pages>1422-1433</pages><issn>1088-9051</issn><eissn>1549-5469</eissn><abstract>Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 (JAK1), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>23788652</pmid><doi>10.1101/gr.154492.113</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1088-9051 |
| ispartof | Genome research, 2013-09, Vol.23 (9), p.1422-1433 |
| issn | 1088-9051 1549-5469 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3759719 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence beta Catenin - genetics Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - virology DNA, Viral - genetics Female Genome, Human Hepatitis B virus Hepatitis B virus - genetics Humans Janus Kinase 1 - genetics Liver Neoplasms - genetics Liver Neoplasms - virology Male Molecular Sequence Data Mutation Sequence Analysis, DNA STAT Transcription Factors - genetics Tumor Suppressor Protein p53 - genetics Virus Integration Wnt Signaling Pathway - genetics |
| title | Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T15%3A06%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Whole-genome%20sequencing%20identifies%20recurrent%20mutations%20in%20hepatocellular%20carcinoma&rft.jtitle=Genome%20research&rft.au=Kan,%20Zhengyan&rft.date=2013-09-01&rft.volume=23&rft.issue=9&rft.spage=1422&rft.epage=1433&rft.pages=1422-1433&rft.issn=1088-9051&rft.eissn=1549-5469&rft_id=info:doi/10.1101/gr.154492.113&rft_dat=%3Cproquest_pubme%3E1429642666%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1429642666&rft_id=info:pmid/23788652&rfr_iscdi=true |