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Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes
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| Zeitschriftentitel: | Molecular Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| In: | Molecular Cancer Research, 15, 2017, 12, S. 1722-1732 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
Zhang, Li MacIsaac, Kenzie D. Zhou, Ting Huang, Pei-Yu Xin, Chunlin Dobson, Jason R. Yu, Kun Chiang, Derek Y. Fan, Yue Pelletier, Marc Wang, Yan Jaeger, Savina Krishnamurthy Radhakrishnan, Viveksagar JeBailey, Lellean Skewes-Cox, Peter Zhang, Jing Fang, Wenfeng Huang, Yan Zhao, Hongyun Zhao, Yuanyuan Li, En Peng, Bin Huang, Alan Dranoff, Glenn Hammerman, Peter S. Engelman, Jeffrey Bitter, Hans Zeng, Yi-Xin Yao, Yao Zhang, Li MacIsaac, Kenzie D. Zhou, Ting Huang, Pei-Yu Xin, Chunlin Dobson, Jason R. Yu, Kun Chiang, Derek Y. Fan, Yue Pelletier, Marc Wang, Yan Jaeger, Savina Krishnamurthy Radhakrishnan, Viveksagar JeBailey, Lellean Skewes-Cox, Peter Zhang, Jing Fang, Wenfeng Huang, Yan Zhao, Hongyun Zhao, Yuanyuan Li, En Peng, Bin Huang, Alan Dranoff, Glenn Hammerman, Peter S. Engelman, Jeffrey Bitter, Hans Zeng, Yi-Xin Yao, Yao |
|---|---|
| author |
Zhang, Li MacIsaac, Kenzie D. Zhou, Ting Huang, Pei-Yu Xin, Chunlin Dobson, Jason R. Yu, Kun Chiang, Derek Y. Fan, Yue Pelletier, Marc Wang, Yan Jaeger, Savina Krishnamurthy Radhakrishnan, Viveksagar JeBailey, Lellean Skewes-Cox, Peter Zhang, Jing Fang, Wenfeng Huang, Yan Zhao, Hongyun Zhao, Yuanyuan Li, En Peng, Bin Huang, Alan Dranoff, Glenn Hammerman, Peter S. Engelman, Jeffrey Bitter, Hans Zeng, Yi-Xin Yao, Yao |
| spellingShingle |
Zhang, Li MacIsaac, Kenzie D. Zhou, Ting Huang, Pei-Yu Xin, Chunlin Dobson, Jason R. Yu, Kun Chiang, Derek Y. Fan, Yue Pelletier, Marc Wang, Yan Jaeger, Savina Krishnamurthy Radhakrishnan, Viveksagar JeBailey, Lellean Skewes-Cox, Peter Zhang, Jing Fang, Wenfeng Huang, Yan Zhao, Hongyun Zhao, Yuanyuan Li, En Peng, Bin Huang, Alan Dranoff, Glenn Hammerman, Peter S. Engelman, Jeffrey Bitter, Hans Zeng, Yi-Xin Yao, Yao Molecular Cancer Research Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes Cancer Research Oncology Molecular Biology |
| author_sort |
zhang, li |
| spelling |
Zhang, Li MacIsaac, Kenzie D. Zhou, Ting Huang, Pei-Yu Xin, Chunlin Dobson, Jason R. Yu, Kun Chiang, Derek Y. Fan, Yue Pelletier, Marc Wang, Yan Jaeger, Savina Krishnamurthy Radhakrishnan, Viveksagar JeBailey, Lellean Skewes-Cox, Peter Zhang, Jing Fang, Wenfeng Huang, Yan Zhao, Hongyun Zhao, Yuanyuan Li, En Peng, Bin Huang, Alan Dranoff, Glenn Hammerman, Peter S. Engelman, Jeffrey Bitter, Hans Zeng, Yi-Xin Yao, Yao 1541-7786 1557-3125 American Association for Cancer Research (AACR) Cancer Research Oncology Molecular Biology http://dx.doi.org/10.1158/1541-7786.mcr-17-0134 <jats:title>Abstract</jats:title> <jats:p>Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-κB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-naïve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFβ pathway activation signature.</jats:p> <jats:p>Implications: This study represents the first integrated analysis of mutation, copy number, and gene expression data in NPC and suggests how tumor genetics and EBV infection influence the tumor microenvironment in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease. Mol Cancer Res; 15(12); 1722–32. ©2017 AACR.</jats:p> Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes Molecular Cancer Research |
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| title |
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_unstemmed |
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_full |
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_fullStr |
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_full_unstemmed |
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_short |
Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_sort |
genomic analysis of nasopharyngeal carcinoma reveals tme-based subtypes |
| topic |
Cancer Research Oncology Molecular Biology |
| url |
http://dx.doi.org/10.1158/1541-7786.mcr-17-0134 |
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2017 |
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1722-1732 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-κB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-naïve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFβ pathway activation signature.</jats:p>
<jats:p>Implications: This study represents the first integrated analysis of mutation, copy number, and gene expression data in NPC and suggests how tumor genetics and EBV infection influence the tumor microenvironment in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease. Mol Cancer Res; 15(12); 1722–32. ©2017 AACR.</jats:p> |
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| author | Zhang, Li, MacIsaac, Kenzie D., Zhou, Ting, Huang, Pei-Yu, Xin, Chunlin, Dobson, Jason R., Yu, Kun, Chiang, Derek Y., Fan, Yue, Pelletier, Marc, Wang, Yan, Jaeger, Savina, Krishnamurthy Radhakrishnan, Viveksagar, JeBailey, Lellean, Skewes-Cox, Peter, Zhang, Jing, Fang, Wenfeng, Huang, Yan, Zhao, Hongyun, Zhao, Yuanyuan, Li, En, Peng, Bin, Huang, Alan, Dranoff, Glenn, Hammerman, Peter S., Engelman, Jeffrey, Bitter, Hans, Zeng, Yi-Xin, Yao, Yao |
| author_facet | Zhang, Li, MacIsaac, Kenzie D., Zhou, Ting, Huang, Pei-Yu, Xin, Chunlin, Dobson, Jason R., Yu, Kun, Chiang, Derek Y., Fan, Yue, Pelletier, Marc, Wang, Yan, Jaeger, Savina, Krishnamurthy Radhakrishnan, Viveksagar, JeBailey, Lellean, Skewes-Cox, Peter, Zhang, Jing, Fang, Wenfeng, Huang, Yan, Zhao, Hongyun, Zhao, Yuanyuan, Li, En, Peng, Bin, Huang, Alan, Dranoff, Glenn, Hammerman, Peter S., Engelman, Jeffrey, Bitter, Hans, Zeng, Yi-Xin, Yao, Yao, Zhang, Li, MacIsaac, Kenzie D., Zhou, Ting, Huang, Pei-Yu, Xin, Chunlin, Dobson, Jason R., Yu, Kun, Chiang, Derek Y., Fan, Yue, Pelletier, Marc, Wang, Yan, Jaeger, Savina, Krishnamurthy Radhakrishnan, Viveksagar, JeBailey, Lellean, Skewes-Cox, Peter, Zhang, Jing, Fang, Wenfeng, Huang, Yan, Zhao, Hongyun, Zhao, Yuanyuan, Li, En, Peng, Bin, Huang, Alan, Dranoff, Glenn, Hammerman, Peter S., Engelman, Jeffrey, Bitter, Hans, Zeng, Yi-Xin, Yao, Yao |
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| description | <jats:title>Abstract</jats:title> <jats:p>Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-κB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-naïve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFβ pathway activation signature.</jats:p> <jats:p>Implications: This study represents the first integrated analysis of mutation, copy number, and gene expression data in NPC and suggests how tumor genetics and EBV infection influence the tumor microenvironment in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease. Mol Cancer Res; 15(12); 1722–32. ©2017 AACR.</jats:p> |
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| spelling | Zhang, Li MacIsaac, Kenzie D. Zhou, Ting Huang, Pei-Yu Xin, Chunlin Dobson, Jason R. Yu, Kun Chiang, Derek Y. Fan, Yue Pelletier, Marc Wang, Yan Jaeger, Savina Krishnamurthy Radhakrishnan, Viveksagar JeBailey, Lellean Skewes-Cox, Peter Zhang, Jing Fang, Wenfeng Huang, Yan Zhao, Hongyun Zhao, Yuanyuan Li, En Peng, Bin Huang, Alan Dranoff, Glenn Hammerman, Peter S. Engelman, Jeffrey Bitter, Hans Zeng, Yi-Xin Yao, Yao 1541-7786 1557-3125 American Association for Cancer Research (AACR) Cancer Research Oncology Molecular Biology http://dx.doi.org/10.1158/1541-7786.mcr-17-0134 <jats:title>Abstract</jats:title> <jats:p>Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-κB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-naïve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFβ pathway activation signature.</jats:p> <jats:p>Implications: This study represents the first integrated analysis of mutation, copy number, and gene expression data in NPC and suggests how tumor genetics and EBV infection influence the tumor microenvironment in this disease. These insights should be considered for guiding immunotherapy treatment strategies in this disease. Mol Cancer Res; 15(12); 1722–32. ©2017 AACR.</jats:p> Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes Molecular Cancer Research |
| spellingShingle | Zhang, Li, MacIsaac, Kenzie D., Zhou, Ting, Huang, Pei-Yu, Xin, Chunlin, Dobson, Jason R., Yu, Kun, Chiang, Derek Y., Fan, Yue, Pelletier, Marc, Wang, Yan, Jaeger, Savina, Krishnamurthy Radhakrishnan, Viveksagar, JeBailey, Lellean, Skewes-Cox, Peter, Zhang, Jing, Fang, Wenfeng, Huang, Yan, Zhao, Hongyun, Zhao, Yuanyuan, Li, En, Peng, Bin, Huang, Alan, Dranoff, Glenn, Hammerman, Peter S., Engelman, Jeffrey, Bitter, Hans, Zeng, Yi-Xin, Yao, Yao, Molecular Cancer Research, Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes, Cancer Research, Oncology, Molecular Biology |
| title | Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_full | Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_fullStr | Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_full_unstemmed | Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_short | Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| title_sort | genomic analysis of nasopharyngeal carcinoma reveals tme-based subtypes |
| title_unstemmed | Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes |
| topic | Cancer Research, Oncology, Molecular Biology |
| url | http://dx.doi.org/10.1158/1541-7786.mcr-17-0134 |