Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer
Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Meth...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/66570 |
| _version_ | 1826188133964709888 |
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| author | Dutt, Amit Ramos, Alex H. Hammerman, Peter S. Mermel, Craig H. Cho, Jeonghee Sharifnia, Tanaz Chande, Ajit Tanaka, Kumiko Elisa Stransky, Nicolas Greulich, Heidi Gray, Nathanael S. Meyerson, Matthew L. |
| author2 | Whitaker College of Health Sciences and Technology |
| author_facet | Whitaker College of Health Sciences and Technology Dutt, Amit Ramos, Alex H. Hammerman, Peter S. Mermel, Craig H. Cho, Jeonghee Sharifnia, Tanaz Chande, Ajit Tanaka, Kumiko Elisa Stransky, Nicolas Greulich, Heidi Gray, Nathanael S. Meyerson, Matthew L. |
| author_sort | Dutt, Amit |
| collection | MIT |
| description | Background
Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma.
Methodology/Principal Findings
Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition.
Conclusions/Significance
These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer. |
| first_indexed | 2024-09-23T07:55:06Z |
| format | Article |
| id | mit-1721.1/66570 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T07:55:06Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/665702022-09-23T09:37:01Z Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer Dutt, Amit Ramos, Alex H. Hammerman, Peter S. Mermel, Craig H. Cho, Jeonghee Sharifnia, Tanaz Chande, Ajit Tanaka, Kumiko Elisa Stransky, Nicolas Greulich, Heidi Gray, Nathanael S. Meyerson, Matthew L. Whitaker College of Health Sciences and Technology Broad Institute of MIT and Harvard Harvard University--MIT Division of Health Sciences and Technology Meyerson, Matthew L. Meyerson, Matthew L. Dutt, Amit Ramos, Alex H. Mermel, Craig H. Tanaka, Kumiko Elisa Stransky, Nicolas Greulich, Heidi Sharifnia, Tanaz Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer. Novartis Pharmaceuticals Corporation American Lung Association Uniting Against Lung Cancer Sara Thomas Monopoli Fund Seaman Foundation India. Dept. of Biotechnology National Lung Cancer Partnership 2011-10-24T21:17:07Z 2011-10-24T21:17:07Z 2011-06 2010-12 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/66570 Dutt, Amit et al. “Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer.” Ed. Ming You. PLoS ONE 6 (2011): e20351. en_US http://dx.doi.org/10.1371/journal.pone.0020351 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Dutt, Amit Ramos, Alex H. Hammerman, Peter S. Mermel, Craig H. Cho, Jeonghee Sharifnia, Tanaz Chande, Ajit Tanaka, Kumiko Elisa Stransky, Nicolas Greulich, Heidi Gray, Nathanael S. Meyerson, Matthew L. Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer |
| title | Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer |
| title_full | Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer |
| title_fullStr | Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer |
| title_full_unstemmed | Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer |
| title_short | Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer |
| title_sort | inhibitor sensitive fgfr1 amplification in human non small cell lung cancer |
| url | http://hdl.handle.net/1721.1/66570 |
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