Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer
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{"title"=>"Inhibitor-sensitive fgfr1 amplification in human non-small cell lung cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Amit", "last_name"=>"Dutt", "scopus_author_id"=>"14059817100"}, {"first_name"=>"Alex H.", "last_name"=>"Ramos", "scopus_author_id"=>"23036507300"}, {"first_name"=>"Peter S.", "last_name"=>"Hammerman", "scopus_author_id"=>"6506925594"}, {"first_name"=>"Craig", "last_name"=>"Mermel", "scopus_author_id"=>"14719873200"}, {"first_name"=>"Jeonghee", "last_name"=>"Cho", "scopus_author_id"=>"54384955900"}, {"first_name"=>"Tanaz", "last_name"=>"Sharifnia", "scopus_author_id"=>"25958419700"}, {"first_name"=>"Ajit", "last_name"=>"Chande", "scopus_author_id"=>"42461167600"}, {"first_name"=>"Kumiko Elisa", "last_name"=>"Tanaka", "scopus_author_id"=>"35977214000"}, {"first_name"=>"Nicolas", "last_name"=>"Stransky", "scopus_author_id"=>"6505983821"}, {"first_name"=>"Heidi", "last_name"=>"Greulich", "scopus_author_id"=>"9737893100"}, {"first_name"=>"Nathanael S.", "last_name"=>"Gray", "scopus_author_id"=>"7201699193"}, {"first_name"=>"Matthew", "last_name"=>"Meyerson", "scopus_author_id"=>"35371816700"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"79958112619", "doi"=>"10.1371/journal.pone.0020351", "issn"=>"19326203", "pui"=>"361908285", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"21666749", "scopus"=>"2-s2.0-79958112619"}, "id"=>"9c54bad3-69d4-3e6c-9d1b-b37f0446ccb8", "abstract"=>"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.\\n\\nMETHODOLOGY/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.\\n\\nCONCLUSIONS/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.", "link"=>"http://www.mendeley.com/research/inhibitorsensitive-fgfr1-amplification-human-nonsmall-cell-lung-cancer", "reader_count"=>111, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>39, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>23, "Student > Postgraduate"=>7, "Student > Master"=>11, "Other"=>10, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>39, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>23, "Student > Postgraduate"=>7, "Student > Master"=>11, "Other"=>10, "Student > Bachelor"=>6, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>14, "Materials Science"=>1, "Medicine and Dentistry"=>27, "Agricultural and Biological Sciences"=>59, "Sports and Recreations"=>1, "Chemistry"=>3, "Computer Science"=>1, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>27}, "Chemistry"=>{"Chemistry"=>3}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>59}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Japan"=>2, "Australia"=>1, "Germany"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/767784"], "description"=>"<p>(A) Bar graph for rescue assay. Lethality due to depleted levels on endogenous FGFR1 level in NCI-H1581 is rescued by over expression of wild type (Wt) full length <i>FGFR1</i> coding sequence . (B) No effect on the survival of NCI-H2170 cells was observed due to over expression of wild type form of FGFR1. NCI-H2170 is not dependent on FGFR1 activity. NI, no infection. shGFP, control hairpin specific for green fluorescent protein used as a negative control. All results are normalized to survival of cells infected with shGFP. Data shown is as mean of three replicates. (C) Validation of FGFR1 rescue by immunoblotting. Depleted levels of endogenous FGFR1 level in NCI-H1581 cells infected with <i>FGFR1</i> shRNA-expressing lentiviruses targeting the FGFR1 3′UTR (lane 1) is rescued by overexpression of wild type form of FGFR1 cDNA lacking the 3′UTR (lane 2) with concomitant modest rescue in the levels tyrosine residue phosphorylation of the FGFR1 substrate FRS2 (middle panel). Actin is shown as a loading control (lower panel).</p>", "links"=>[], "tags"=>["coding", "rescues", "lethality", "shrna", "targeting"], "article_id"=>438144, "categories"=>["Cancer", "Genetics"], "users"=>["Amit Dutt", "Alex H. Ramos", "Peter S. Hammerman", "Craig Mermel", "Jeonghee Cho", "Tanaz Sharifnia", "Ajit Chande", "Kumiko Elisa Tanaka", "Nicolas Stransky", "Heidi Greulich", "Nathanael S. Gray", "Matthew Meyerson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020351.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ectopic_expression_of_FGFR1_coding_region_rescues_lethality_of_an_shRNA_targeting_the_FGFR1_3_UTR_/438144", "title"=>"Ectopic expression of <i>FGFR1</i> coding region rescues lethality of an shRNA targeting the <i>FGFR1</i> 3′ UTR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-07 02:15:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/385899", "https://ndownloader.figshare.com/files/385925", "https://ndownloader.figshare.com/files/385953", "https://ndownloader.figshare.com/files/385980", "https://ndownloader.figshare.com/files/386011", "https://ndownloader.figshare.com/files/386046", "https://ndownloader.figshare.com/files/386069", "https://ndownloader.figshare.com/files/386088", "https://ndownloader.figshare.com/files/386099", "https://ndownloader.figshare.com/files/386114"], "description"=>"<div><h3>Background</h3><p>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.</p> <h3>Methodology/Principal Findings</h3><p>Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–<em>WHSC1L1</em>, <em>LETM2</em>, and <em>FGFR1</em>–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 <em>FGFR1</em> is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with <em>FGFR1</em>-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition.</p> <h3>Conclusions/Significance</h3><p>These studies show that <em>FGFR1</em> amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.</p> </div>", "links"=>[], "tags"=>["inhibitor-sensitive", "amplification", "non-small", "cancer"], "article_id"=>136171, "categories"=>["Cancer", "Genetics"], "users"=>["Amit Dutt", "Alex H. Ramos", "Peter S. Hammerman", "Craig Mermel", "Jeonghee Cho", "Tanaz Sharifnia", "Ajit Chande", "Kumiko Elisa Tanaka", "Nicolas Stransky", "Heidi Greulich", "Nathanael S. Gray", "Matthew Meyerson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0020351.s001", "https://dx.doi.org/10.1371/journal.pone.0020351.s002", "https://dx.doi.org/10.1371/journal.pone.0020351.s003", "https://dx.doi.org/10.1371/journal.pone.0020351.s004", "https://dx.doi.org/10.1371/journal.pone.0020351.s005", "https://dx.doi.org/10.1371/journal.pone.0020351.s006", "https://dx.doi.org/10.1371/journal.pone.0020351.s007", "https://dx.doi.org/10.1371/journal.pone.0020351.s008", "https://dx.doi.org/10.1371/journal.pone.0020351.s009", "https://dx.doi.org/10.1371/journal.pone.0020351.s010"], "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Inhibitor_Sensitive_FGFR1_Amplification_in_Human_Non_Small_Cell_Lung_Cancer/136171", "title"=>"Inhibitor-Sensitive <em>FGFR1</em> Amplification in Human Non-Small Cell Lung Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-06-07 01:42:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/767572"], "description"=>"<p>(A) Copy number estimates at chromosome arm 8p11-12q for 44 NSCLC samples (columns; ordered by amplification of 8p11) having amplification greater than 3.25 copies (log2 ratio of 0.7) from a collection of 732 NSCLC primary samples and cell lines. The horizontal line indicates the region containing <i>FGFR1</i>, <i>LETM2</i> and <i>WHSC1L1</i> genes. The color scale ranges from blue (deletion) to red (amplification) with estimated copy numbers shown. Grey regions represent the absence of SNP copy number data. (B) Bar graph depicting percentages of samples harboring 8p11-12 amplification in lung adenocarcinomas (AC) and squamous cell carcinoma (SCC) demonstrates that <i>FGFR1</i> amplification is observed in SCC at much higher frequency than AC. (C) FGFR1 expression (upper panel) shown in ten NSCLC cells; eight cell lines harboring <i>FGFR1</i> amplification—HCC1734, HCC95, NCI-H2444, Calu3, NCI-H2077, NCI-H1703, NCI-H1581 and NCI-H520 (indicated by red horizontal bar below)—one NSCLC cell line harboring deletion of the region HCC15 (indicated by blue horizontal bar below)– and three NSCLC cells with no amplification—A427, NCI-H226, NCI-H2170 (indicated by black horizontal bar below)– using actin as a loading control (shown in lower panel). <i>FGFR1</i> copy number status and 8p11-12 amplicon length determined by SNP array is indicated below cells harboring amplification. Of note, NCI-H2077 and NCI-1581 were found to be genotypically identical by fingerprinting analysis.</p>", "links"=>[], "tags"=>["locus"], "article_id"=>437937, "categories"=>["Cancer", "Genetics"], "users"=>["Amit Dutt", "Alex H. Ramos", "Peter S. Hammerman", "Craig Mermel", "Jeonghee Cho", "Tanaz Sharifnia", "Ajit Chande", "Kumiko Elisa Tanaka", "Nicolas Stransky", "Heidi Greulich", "Nathanael S. Gray", "Matthew Meyerson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020351.g001", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amplifications_of_FGFR1_locus_in_NSCLC_/437937", "title"=>"Amplifications of <i>FGFR1</i> locus in NSCLC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-07 02:12:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/767689"], "description"=>"<p>(A) Effects of five <i>FGFR1</i> shRNA constructs on FGFR1 protein expression in NCI-H1581 cells as assayed by immunoblotting. shRNAs #1, #2 and #5 efficiently knock down endogenous FGFR1 expression in NCI-H1581 cells infected with shRNA-expressing lentiviruses while shRNAs #3 and #4 do not. Actin is shown as a loading control (lower panel). <i>(B</i> and <i>C)</i>, infection with three independent FGFR1-suppressing hairpins (#1, #2 and #5) inhibits survival of NCI-H1581 cells over expressing <i>FGFR1</i> (B) but did not inhibit survival of cells not harboring <i>FGFR1</i> amplification, NCI-H2170 (C) as assessed by WST assay. NI, no infection. shGFP, control hairpin specific for green fluorescent protein used as a negative control. All results normalized to survival of cells infected with shGFP.</p>", "links"=>[], "tags"=>["cells", "knock-down", "fgfr1"], "article_id"=>438050, "categories"=>["Cancer", "Genetics"], "users"=>["Amit Dutt", "Alex H. Ramos", "Peter S. Hammerman", "Craig Mermel", "Jeonghee Cho", "Tanaz Sharifnia", "Ajit Chande", "Kumiko Elisa Tanaka", "Nicolas Stransky", "Heidi Greulich", "Nathanael S. Gray", "Matthew Meyerson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020351.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NCI_H1581_cells_are_sensitive_to_knock_down_of_FGFR1_expression_/438050", "title"=>"NCI-H1581 cells are sensitive to knock-down of FGFR1 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-07 02:14:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/767883"], "description"=>"<p>(A) Treatment with the indicated concentrations of pan FGFR inhibitor PD173074 inhibited soft agar colony formation by the NCI-H1581 NSCLC cell lines harboring <i>FGFR1</i> amplification, as compared with the NCI-H2170 line, which does not harbor <i>FGFR1</i> amplification. Colonies were photographed and quantitated after 4 weeks. (B) Treatment with the indicated concentrations of PD173074 inhibited survival of NCI-H1581 cells, but not of NCI-H2170 cells, as determined by WST assay performed after 4 days treatment. IC50s are indicated.</p>", "links"=>[], "tags"=>["tyrosine", "kinase", "nci-h1581"], "article_id"=>438242, "categories"=>["Cancer", "Genetics"], "users"=>["Amit Dutt", "Alex H. Ramos", "Peter S. Hammerman", "Craig Mermel", "Jeonghee Cho", "Tanaz Sharifnia", "Ajit Chande", "Kumiko Elisa Tanaka", "Nicolas Stransky", "Heidi Greulich", "Nathanael S. Gray", "Matthew Meyerson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020351.g004", "stats"=>{"downloads"=>2, "page_views"=>70, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_FGFR1_tyrosine_kinase_activity_is_essential_in_NCI_H1581_cells_/438242", "title"=>"FGFR1 tyrosine kinase activity is essential in NCI-H1581 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-07 02:17:22"}

PMC Usage Stats | Further Information

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