Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability
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{"title"=>"Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability", "type"=>"journal", "authors"=>[{"first_name"=>"Kelsie L.", "last_name"=>"Thu", "scopus_author_id"=>"26432362800"}, {"first_name"=>"Emily A.", "last_name"=>"Vucic", "scopus_author_id"=>"12754028200"}, {"first_name"=>"Raj", "last_name"=>"Chari", "scopus_author_id"=>"11939421400"}, {"first_name"=>"Wei", "last_name"=>"Zhang", "scopus_author_id"=>"49664602100"}, {"first_name"=>"William W.", "last_name"=>"Lockwood", "scopus_author_id"=>"11939640000"}, {"first_name"=>"John C.", "last_name"=>"English", "scopus_author_id"=>"7202807133"}, {"first_name"=>"Rong", "last_name"=>"Fu", "scopus_author_id"=>"37064308000"}, {"first_name"=>"Pei", "last_name"=>"Wang", "scopus_author_id"=>"55865567238"}, {"first_name"=>"Ziding", "last_name"=>"Feng", "scopus_author_id"=>"7403442940"}, {"first_name"=>"Calum E.", "last_name"=>"MacAulay", "scopus_author_id"=>"35370099900"}, {"first_name"=>"Adi F.", "last_name"=>"Gazdar", "scopus_author_id"=>"35372587300"}, {"first_name"=>"Stephen", "last_name"=>"Lam", "scopus_author_id"=>"55193690600"}, {"first_name"=>"Wan L.", "last_name"=>"Lam", "scopus_author_id"=>"7203021871"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84863273943", "doi"=>"10.1371/journal.pone.0033003", "pui"=>"364373912", "pmid"=>"22412972", "scopus"=>"2-s2.0-84863273943", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"ae70a2c2-4885-3622-821f-6f7cdd44e3a1", "abstract"=>"Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.", "link"=>"http://www.mendeley.com/research/lung-adenocarcinoma-never-smokers-smokers-harbor-differential-regions-genetic-alteration-exhibit-dif", "reader_count"=>31, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>3, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>3, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>12, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>1, "Computer Science"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>2}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/345019", "https://ndownloader.figshare.com/files/345046", "https://ndownloader.figshare.com/files/345090", "https://ndownloader.figshare.com/files/345155", "https://ndownloader.figshare.com/files/345235", "https://ndownloader.figshare.com/files/345294", "https://ndownloader.figshare.com/files/345361", "https://ndownloader.figshare.com/files/345407", "https://ndownloader.figshare.com/files/345529", "https://ndownloader.figshare.com/files/345610"], "description"=>"<div><p>Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as <em>EGFR</em>, <em>EML4-ALK</em>, and <em>KRAS</em>, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS.</p> <p>High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.</p> </div>", "links"=>[], "tags"=>["adenocarcinoma", "smokers", "harbor", "differential", "regions", "alteration", "levels", "genomic", "instability"], "article_id"=>128204, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0033003.s001", "https://dx.doi.org/10.1371/journal.pone.0033003.s002", "https://dx.doi.org/10.1371/journal.pone.0033003.s003", "https://dx.doi.org/10.1371/journal.pone.0033003.s004", "https://dx.doi.org/10.1371/journal.pone.0033003.s005", "https://dx.doi.org/10.1371/journal.pone.0033003.s006", "https://dx.doi.org/10.1371/journal.pone.0033003.s007", "https://dx.doi.org/10.1371/journal.pone.0033003.s008", "https://dx.doi.org/10.1371/journal.pone.0033003.s009", "https://dx.doi.org/10.1371/journal.pone.0033003.s010"], "stats"=>{"downloads"=>7, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Lung_Adenocarcinoma_of_Never_Smokers_and_Smokers_Harbor_Differential_Regions_of_Genetic_Alteration_and_Exhibit_Different_Levels_of_Genomic_Instability/128204", "title"=>"Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-03-07 02:16:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/671716"], "description"=>"<p>Proportion of genome altered in smokers and never smokers.</p>", "links"=>[], "tags"=>["genome", "altered", "smokers"], "article_id"=>342196, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.t002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proportion_of_genome_altered_in_smokers_and_never_smokers_/342196", "title"=>"Proportion of genome altered in smokers and never smokers.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-07 00:36:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/671284"], "description"=>"<p>In both the BCCA (n = 69) and MSKCC (n = 66) datasets, <i>EGFR</i> and <i>KRAS</i> mutations are more prevalent in NS and smokers, respectively, consistent with the literature (A, B). The PGA in NS was greater than that of smokers in the BCCA and MSKCC tumors (C, D). PGA was also greater in <i>EGFR</i>-mutant versus <i>EGFR</i>-wild type tumors in both datasets (E,F), corroborating the difference we identified in smoker and NS tumors, as NS tumors are enriched for <i>EGFR</i> mutations.</p>", "links"=>[], "tags"=>["mutation", "frequencies", "pga", "bcca", "mskcc"], "article_id"=>341748, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.g001", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_EGFR_and_KRAS_mutation_frequencies_and_PGA_in_the_BCCA_and_MSKCC_tumors_/341748", "title"=>"<i>EGFR</i> and <i>KRAS</i> mutation frequencies and PGA in the BCCA and MSKCC tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-07 00:29:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/671608"], "description"=>"<p>Minimal common regions of differential alteration between smokers and never smokers in three independent datasets.</p>", "links"=>[], "tags"=>["regions", "differential", "alteration", "smokers"], "article_id"=>342082, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.t004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Minimal_common_regions_of_differential_alteration_between_smokers_and_never_smokers_in_three_independent_datasets_/342082", "title"=>"Minimal common regions of differential alteration between smokers and never smokers in three independent datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-07 00:34:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/671764"], "description"=>"*<p>The proportion of individuals of Asian descent in our NS smoker cohort was significantly greater than that of smokers. However, a recent study investigating genomic differences in Western European versus East-Asian lung adenocarcinomas reported no difference in PGA <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033003#pone.0033003-Broet1\" target=\"_blank\">[6]</a>. Nonetheless, our validation cohorts from MSKCC and TSP were from geographically distant research centers, whose patient demographics (including race) likely differ from our own.</p>**<p>One pack year is defined as smoking one package of cigarettes every day for one year.</p>", "links"=>[], "tags"=>["adenocarcinoma", "tumors"], "article_id"=>342242, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_data_for_lung_adenocarcinoma_tumors_sampled_/342242", "title"=>"Demographic data for lung adenocarcinoma tumors sampled.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-07 00:37:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/671528"], "description"=>"<p>Frequencies of copy number alteration for 9 genes commonly reported as disrupted in lung adenocarcinoma are shown. The difference in frequencies of alteration in smokers and NS was not statistically different for any of these genes, suggesting they are equally important in lung adenocarcinoma tumorigenesis in both smokers and NS. Fisher's exact test p-values for the comparison of alteration frequencies in NS and smokers are indicated for each gene.</p>", "links"=>[], "tags"=>["disrupted", "smokers"], "article_id"=>342006, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.g003", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_commonly_disrupted_in_smokers_and_NS_/342006", "title"=>"Genes commonly disrupted in smokers and NS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-07 00:33:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/671668"], "description"=>"<p>Minimal common regions of differential alteration between smokers and never smokers in BCCA and MSKCC datasets.</p>", "links"=>[], "tags"=>["regions", "differential", "alteration", "smokers", "bcca", "mskcc"], "article_id"=>342131, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.t003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Minimal_common_regions_of_differential_alteration_between_smokers_and_never_smokers_in_BCCA_and_MSKCC_datasets_/342131", "title"=>"Minimal common regions of differential alteration between smokers and never smokers in BCCA and MSKCC datasets.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-07 00:35:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/671380"], "description"=>"<p>The frequency of copy number alterations throughout the genome is depicted for smokers (A) and NS (B) tumors. Frequencies were calculated using a moving average window size of 500 SNP array probes. Each vertical box represents a single chromosome with the hashed line indicating the centromere. The genomic locations of the differentially altered regions (n = 313) identified in the BCCA tumors are indicated in plot C. Red bars indicate NS-specific regions and blue bars indicate smoker-specific regions.</p>", "links"=>[], "tags"=>["landscapes", "bcca", "ns", "smoker"], "article_id"=>341855, "categories"=>["Cancer", "Biological Sciences", "Genetics"], "users"=>["Kelsie L. Thu", "Emily A. Vucic", "Raj Chari", "Wei Zhang", "William W. Lockwood", "John C. English", "Rong Fu", "Pei Wang", "Ziding Feng", "Calum E. MacAulay", "Adi F. Gazdar", "Stephen Lam", "Wan L. Lam"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0033003.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genomic_landscapes_of_the_BCCA_NS_and_smoker_lung_adenocarcinomas_/341855", "title"=>"Genomic landscapes of the BCCA NS and smoker lung adenocarcinomas.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-07 00:30:55"}

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Relative Metric

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