Cargando…
The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics
Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648877/ https://www.ncbi.nlm.nih.gov/pubmed/34873156 http://dx.doi.org/10.1038/s41467-021-27341-1 |
| _version_ | 1784610902118498304 |
|---|---|
| author | Tang, Ming Abbas, Hussein A. Negrao, Marcelo V. Ramineni, Maheshwari Hu, Xin Hubert, Shawna Marie Fujimoto, Junya Reuben, Alexandre Varghese, Susan Zhang, Jianhua Li, Jun Chow, Chi-Wan Mao, Xizeng Song, Xingzhi Lee, Won-Chul Wu, Jia Little, Latasha Gumbs, Curtis Behrens, Carmen Moran, Cesar Weissferdt, Annikka Lee, J. Jack Sepesi, Boris Swisher, Stephen Cheng, Chao Kurie, Jonathan Gibbons, Don Heymach, John V. Wistuba, Ignacio I. Futreal, P. Andrew Kalhor, Neda Zhang, Jianjun |
| author_facet | Tang, Ming Abbas, Hussein A. Negrao, Marcelo V. Ramineni, Maheshwari Hu, Xin Hubert, Shawna Marie Fujimoto, Junya Reuben, Alexandre Varghese, Susan Zhang, Jianhua Li, Jun Chow, Chi-Wan Mao, Xizeng Song, Xingzhi Lee, Won-Chul Wu, Jia Little, Latasha Gumbs, Curtis Behrens, Carmen Moran, Cesar Weissferdt, Annikka Lee, J. Jack Sepesi, Boris Swisher, Stephen Cheng, Chao Kurie, Jonathan Gibbons, Don Heymach, John V. Wistuba, Ignacio I. Futreal, P. Andrew Kalhor, Neda Zhang, Jianjun |
| author_sort | Tang, Ming |
| collection | PubMed |
| description | Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors. |
| format | Online Article Text |
| id | pubmed-8648877 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-86488772021-12-27 The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics Tang, Ming Abbas, Hussein A. Negrao, Marcelo V. Ramineni, Maheshwari Hu, Xin Hubert, Shawna Marie Fujimoto, Junya Reuben, Alexandre Varghese, Susan Zhang, Jianhua Li, Jun Chow, Chi-Wan Mao, Xizeng Song, Xingzhi Lee, Won-Chul Wu, Jia Little, Latasha Gumbs, Curtis Behrens, Carmen Moran, Cesar Weissferdt, Annikka Lee, J. Jack Sepesi, Boris Swisher, Stephen Cheng, Chao Kurie, Jonathan Gibbons, Don Heymach, John V. Wistuba, Ignacio I. Futreal, P. Andrew Kalhor, Neda Zhang, Jianjun Nat Commun Article Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors. Nature Publishing Group UK 2021-12-06 /pmc/articles/PMC8648877/ /pubmed/34873156 http://dx.doi.org/10.1038/s41467-021-27341-1 Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Tang, Ming Abbas, Hussein A. Negrao, Marcelo V. Ramineni, Maheshwari Hu, Xin Hubert, Shawna Marie Fujimoto, Junya Reuben, Alexandre Varghese, Susan Zhang, Jianhua Li, Jun Chow, Chi-Wan Mao, Xizeng Song, Xingzhi Lee, Won-Chul Wu, Jia Little, Latasha Gumbs, Curtis Behrens, Carmen Moran, Cesar Weissferdt, Annikka Lee, J. Jack Sepesi, Boris Swisher, Stephen Cheng, Chao Kurie, Jonathan Gibbons, Don Heymach, John V. Wistuba, Ignacio I. Futreal, P. Andrew Kalhor, Neda Zhang, Jianjun The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| title | The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| title_full | The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| title_fullStr | The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| title_full_unstemmed | The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| title_short | The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| title_sort | histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648877/ https://www.ncbi.nlm.nih.gov/pubmed/34873156 http://dx.doi.org/10.1038/s41467-021-27341-1 |
| work_keys_str_mv | AT tangming thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT abbashusseina thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT negraomarcelov thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT raminenimaheshwari thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT huxin thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT hubertshawnamarie thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT fujimotojunya thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT reubenalexandre thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT varghesesusan thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT zhangjianhua thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT lijun thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT chowchiwan thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT maoxizeng thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT songxingzhi thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT leewonchul thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT wujia thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT littlelatasha thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT gumbscurtis thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT behrenscarmen thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT morancesar thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT weissferdtannikka thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT leejjack thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT sepesiboris thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT swisherstephen thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT chengchao thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT kuriejonathan thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT gibbonsdon thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT heymachjohnv thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT wistubaignacioi thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT futrealpandrew thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT kalhorneda thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT zhangjianjun thehistologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT tangming histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT abbashusseina histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT negraomarcelov histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT raminenimaheshwari histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT huxin histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT hubertshawnamarie histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT fujimotojunya histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT reubenalexandre histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT varghesesusan histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT zhangjianhua histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT lijun histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT chowchiwan histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT maoxizeng histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT songxingzhi histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT leewonchul histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT wujia histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT littlelatasha histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT gumbscurtis histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT behrenscarmen histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT morancesar histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT weissferdtannikka histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT leejjack histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT sepesiboris histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT swisherstephen histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT chengchao histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT kuriejonathan histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT gibbonsdon histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT heymachjohnv histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT wistubaignacioi histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT futrealpandrew histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT kalhorneda histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics AT zhangjianjun histologicphenotypeoflungcancersisassociatedwithtranscriptomicfeaturesratherthangenomiccharacteristics |