The Genomic Landscape of TP53 and p53 Annotated High Grade Ovarian Serous Carcinomas from a Defined Founder Population Associated with Patient Outcome
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{"title"=>"The Genomic Landscape of TP53 and p53 Annotated High Grade Ovarian Serous Carcinomas from a Defined Founder Population Associated with Patient Outcome", "type"=>"journal", "authors"=>[{"first_name"=>"Paulina M.", "last_name"=>"Wojnarowicz", "scopus_author_id"=>"24802771200"}, {"first_name"=>"Kathleen Klein", "last_name"=>"Oros", "scopus_author_id"=>"8718962000"}, {"first_name"=>"Michael C J", "last_name"=>"Quinn", "scopus_author_id"=>"15833001200"}, {"first_name"=>"Suzanna L.", "last_name"=>"Arcand", "scopus_author_id"=>"6508116252"}, {"first_name"=>"Karen", "last_name"=>"Gambaro", "scopus_author_id"=>"15848130800"}, {"first_name"=>"Jason", "last_name"=>"Madore", "scopus_author_id"=>"12776042500"}, {"first_name"=>"Ashley H.", "last_name"=>"Birch", "scopus_author_id"=>"23466340700"}, {"first_name"=>"Manon", "last_name"=>"de Ladurantaye", "scopus_author_id"=>"6507117543"}, {"first_name"=>"Kurosh", "last_name"=>"Rahimi", "scopus_author_id"=>"27068012200"}, {"first_name"=>"Diane M.", "last_name"=>"Provencher", "scopus_author_id"=>"7003694463"}, {"first_name"=>"Anne Marie", "last_name"=>"Mes-Masson", "scopus_author_id"=>"7003842511"}, {"first_name"=>"Celia M T", "last_name"=>"Greenwood", "scopus_author_id"=>"34570534700"}, {"first_name"=>"Patricia N.", "last_name"=>"Tonin", "scopus_author_id"=>"7006990980"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84866682056", "pui"=>"365718470", "doi"=>"10.1371/journal.pone.0045484", "sgr"=>"84866682056", "pmid"=>"23029043", "issn"=>"19326203"}, "id"=>"b73f37fc-7acf-38e5-a220-88c9a6425d9b", "abstract"=>"High-grade ovarian serous carcinomas (HGSC) are characterized by TP53 mutations and non-random patterns of chromosomal anomalies, where the nature of the TP53 mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically defined populations has not been explored. Whole genome SNP array, and TP53 mutation, gene and protein expression analyses were assessed in 87 confirmed HGSC samples with clinical correlates from French Canadians, a population exhibiting strong founder effects, and results were compared with independent reports describing similar analyses from unselected populations. TP53 mutations were identified in 91% of HGSCs. Anomalies observed in more than 50% of TP53 mutation-positive HGSCs involved gains of 3q, 8q and 20q, and losses of 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 22q and Xp. Nearly 400 regions of non-overlapping amplification or deletion were identified, where 178 amplifications and 98 deletions involved known genes. The subgroup expressing mutant p53 protein exhibited significantly prolonged overall and disease-free survival as compared with the p53 protein null subgroup. Interestingly, a comparative analysis of genomic landscapes revealed a significant enrichment of gains involving 1q, 8q, and 12p intervals in the subgroup expressing mutant p53 protein as compared with the p53 protein null subgroup. Although the findings show that the frequency of TP53 mutations and the genomic landscapes observed in French Canadian samples were similar to those reported for samples from unselected populations, there were differences in the magnitude of global gains/losses of specific chromosomal arms and in the spectrum of amplifications and deletions involving focal regions in individual samples. The findings from our comparative genomic analyses also support the notion that there may be biological differences between HGSCs that could be related to the nature of the TP53 mutation.", "link"=>"http://www.mendeley.com/research/genomic-landscape-tp53-p53-annotated-high-grade-ovarian-serous-carcinomas-defined-founder-population", "reader_count"=>19, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Mathematics"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Mathematics"=>{"Mathematics"=>1}}, "reader_count_by_country"=>{"Canada"=>2, "Norway"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/572954"], "description"=>"<p>Percentage of the 79 <i>TP53</i> mutation-positive HGSCs with chromosomal anomalies, including copy number alteration and allelic imbalance, and breaks occurring per chromosome arm, as inferred by reviewing image files created by the Genome Viewer module in BeadStudio Data Analysis software v2.2.22. The chromosome arms are arranged according to their size in megabases, left to right from smallest to largest.</p>", "links"=>[], "tags"=>["anomalies", "breaks", "genome", "mutation-positive", "hgsc"], "article_id"=>243427, "categories"=>["Cancer", "Genetics"], "users"=>["Paulina M. Wojnarowicz", "Kathleen Klein Oros", "Michael C. J. Quinn", "Suzanna L. Arcand", "Karen Gambaro", "Jason Madore", "Ashley H. Birch", "Manon de Ladurantaye", "Kurosh Rahimi", "Diane M. Provencher", "Anne-Marie Mes-Masson", "Celia M. T. Greenwood", "Patricia N. Tonin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045484.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosomal_anomalies_and_breaks_across_the_genome_of_TP53_mutation_positive_HGSC_cases_/243427", "title"=>"Chromosomal anomalies and breaks across the genome of <i>TP53</i> mutation-positive HGSC cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-20 00:57:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/573034"], "description"=>"<p>Global regions of gain and loss in the 79 <i>TP53</i> mutation-positive HGSC cases, as determined by GenoCNA analyses (A). Regions of gain and loss occurring in >50% of the 79 HGSC cases are indicated by green arrowheads. Regions of gain and loss occurring in >50% of the TCGA samples <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045484#pone.0045484-TCGA1\" target=\"_blank\">[8]</a> and in >39% of the AOCS samples <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045484#pone.0045484-Gorringe1\" target=\"_blank\">[9]</a> are indicated by solid and dashed arrows, respectively (red colour indicates gain, blue colour indicates loss). Global regions of gain and loss in the 44 HGSC cases expressing p53 mutant protein (B). Global regions of gain and loss in the 24 p53 protein null HGSCs (C). Regions found to be significantly gained in the cases expressing p53 mutant protein as compared to the p53 protein null cases by GenoCNA analyses include 1q, 8q and 12p, and are indicated by purple arrows.</p>", "links"=>[], "tags"=>["regions", "mutation-positive", "hgsc"], "article_id"=>243522, "categories"=>["Cancer", "Genetics"], "users"=>["Paulina M. Wojnarowicz", "Kathleen Klein Oros", "Michael C. J. Quinn", "Suzanna L. Arcand", "Karen Gambaro", "Jason Madore", "Ashley H. Birch", "Manon de Ladurantaye", "Kurosh Rahimi", "Diane M. Provencher", "Anne-Marie Mes-Masson", "Celia M. T. Greenwood", "Patricia N. Tonin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045484.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Global_regions_of_gain_and_loss_in_TP53_mutation_positive_HGSC_cases_/243522", "title"=>"Global regions of gain and loss in <i>TP53</i> mutation-positive HGSC cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-20 00:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/573177"], "description"=>"<p>GenoCNA analysis of Chromosome 17 copy number alterations in the 79 <i>TP53</i> mutation-positive HGSC cases. The genomic loci of the genes <i>TP53</i>, <i>NF1</i>, and <i>BRCA1</i> are indicated with arrows. CN, copy number; LOH, loss of heterozygosity.</p>", "links"=>[], "tags"=>["17", "alterations", "mutation-positive", "hgsc"], "article_id"=>243658, "categories"=>["Cancer", "Genetics"], "users"=>["Paulina M. Wojnarowicz", "Kathleen Klein Oros", "Michael C. J. Quinn", "Suzanna L. Arcand", "Karen Gambaro", "Jason Madore", "Ashley H. Birch", "Manon de Ladurantaye", "Kurosh Rahimi", "Diane M. Provencher", "Anne-Marie Mes-Masson", "Celia M. T. Greenwood", "Patricia N. Tonin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045484.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosome_17_copy_number_alterations_in_TP53_mutation_positive_HGSC_cases_/243658", "title"=>"Chromosome 17 copy number alterations in <i>TP53</i> mutation-positive HGSC cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-20 01:00:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/303430", "https://ndownloader.figshare.com/files/303453", "https://ndownloader.figshare.com/files/303473", "https://ndownloader.figshare.com/files/303503", "https://ndownloader.figshare.com/files/303520", "https://ndownloader.figshare.com/files/303541", "https://ndownloader.figshare.com/files/303553"], "description"=>"<div><p>High-grade ovarian serous carcinomas (HGSC) are characterized by <em>TP53</em> mutations and non-random patterns of chromosomal anomalies, where the nature of the <em>TP53</em> mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically defined populations has not been explored. Whole genome SNP array, and <em>TP53</em> mutation, gene and protein expression analyses were assessed in 87 confirmed HGSC samples with clinical correlates from French Canadians, a population exhibiting strong founder effects, and results were compared with independent reports describing similar analyses from unselected populations. <em>TP53</em> mutations were identified in 91% of HGSCs. Anomalies observed in more than 50% of <em>TP53</em> mutation-positive HGSCs involved gains of 3q, 8q and 20q, and losses of 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 22q and Xp. Nearly 400 regions of non-overlapping amplification or deletion were identified, where 178 amplifications and 98 deletions involved known genes. The subgroup expressing mutant p53 protein exhibited significantly prolonged overall and disease-free survival as compared with the p53 protein null subgroup. Interestingly, a comparative analysis of genomic landscapes revealed a significant enrichment of gains involving 1q, 8q, and 12p intervals in the subgroup expressing mutant p53 protein as compared with the p53 protein null subgroup. Although the findings show that the frequency of <em>TP53</em> mutations and the genomic landscapes observed in French Canadian samples were similar to those reported for samples from unselected populations, there were differences in the magnitude of global gains/losses of specific chromosomal arms and in the spectrum of amplifications and deletions involving focal regions in individual samples. The findings from our comparative genomic analyses also support the notion that there may be biological differences between HGSCs that could be related to the nature of the <em>TP53</em> mutation.</p> </div>", "links"=>[], "tags"=>["genomic", "p53", "annotated", "ovarian", "serous", "carcinomas", "defined"], "article_id"=>119831, "categories"=>["Cancer", "Genetics"], "users"=>["Paulina M. Wojnarowicz", "Kathleen Klein Oros", "Michael C. J. Quinn", "Suzanna L. Arcand", "Karen Gambaro", "Jason Madore", "Ashley H. Birch", "Manon de Ladurantaye", "Kurosh Rahimi", "Diane M. Provencher", "Anne-Marie Mes-Masson", "Celia M. T. Greenwood", "Patricia N. Tonin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0045484.s001", "https://dx.doi.org/10.1371/journal.pone.0045484.s002", "https://dx.doi.org/10.1371/journal.pone.0045484.s003", "https://dx.doi.org/10.1371/journal.pone.0045484.s004", "https://dx.doi.org/10.1371/journal.pone.0045484.s005", "https://dx.doi.org/10.1371/journal.pone.0045484.s006", "https://dx.doi.org/10.1371/journal.pone.0045484.s007"], "stats"=>{"downloads"=>24, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Genomic_Landscape_of_TP53_and_p53_Annotated_High_Grade_Ovarian_Serous_Carcinomas_from_a_Defined_Founder_Population_Associated_with_Patient_Outcome/119831", "title"=>"The Genomic Landscape of <em>TP53</em> and p53 Annotated High Grade Ovarian Serous Carcinomas from a Defined Founder Population Associated with Patient Outcome", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-20 02:43:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/573285"], "description"=>"<p>GenoCNA analysis comparing the mean copy number, on a per SNP basis, of the 44 samples expressing p53 mutant protein to that of the 24 p53 protein null HGSC cases for chromosomes 1 (A), 8 (B) and 12 (C), which contain regions significantly gained in the HGSC cases expressing p53 mutant protein as compared to the p53 protein null HGSC cases (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045484#pone-0045484-g003\" target=\"_blank\">Figure 3B, C</a>). Points on the plot represent –log10 of p-values from t-tests comparing the means in the two groups. Blue bars indicate regions of significant gain.</p>", "links"=>[], "tags"=>["comparing", "hgsc", "cases", "p53"], "article_id"=>243766, "categories"=>["Cancer", "Genetics"], "users"=>["Paulina M. Wojnarowicz", "Kathleen Klein Oros", "Michael C. J. Quinn", "Suzanna L. Arcand", "Karen Gambaro", "Jason Madore", "Ashley H. Birch", "Manon de Ladurantaye", "Kurosh Rahimi", "Diane M. Provencher", "Anne-Marie Mes-Masson", "Celia M. T. Greenwood", "Patricia N. Tonin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045484.g005", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GenoCNA_analysis_comparing_HGSC_cases_based_on_p53_immunoreactivity_/243766", "title"=>"GenoCNA analysis comparing HGSC cases based on p53 immunoreactivity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-20 01:02:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/572783"], "description"=>"<p>Ziplex® custom array-derived <i>TP53</i> gene expression data for 76 of the 87 HGSC cases, grouped according to <i>TP53</i> mutation type (A). The mean <i>TP53</i> gene expression values for missense (n = 45), frameshift (n = 9), splice (n = 7), nonsense (n = 6), in-frame insertion (n = 1) and mutation-negative (n = 8) HGSC cases are 232.2, 67.6, 70.1, 46.6, 148.9, and 114.5, respectively, as indicated by arrows. Immunohistochemistry analysis of 76 HGSC cores, arrayed on a tissue microarray, grouped according to <i>TP53</i> mutation type (B). Positive p53 immunoreactivity was observed for 42/45 missense, 1/9 frameshift, 0/7 splice, 0/6 nonsense, 1/1 in-frame insertion, and 3/8 mutation-negative HGSC cases. Kaplan-Meier survival curve analysis of <i>TP53</i> mutation-positive HGSC cases for overall survival, in months, of patients positive for p53 staining (n = 44) compared to patients negative for p53 staining (n = 24) (C). Kaplan-Meier survival curve analysis of <i>TP53</i> mutation-positive HGSC cases for disease-free interval, in months, of patients positive for p53 staining (n = 44) compared to patients negative for p53 staining (n = 24) (D). Indicated p-values were derived from Mantel-Cox, log-rank tests.</p>", "links"=>[], "tags"=>["kaplan-meier", "analyses", "hgsc"], "article_id"=>243263, "categories"=>["Cancer", "Genetics"], "users"=>["Paulina M. Wojnarowicz", "Kathleen Klein Oros", "Michael C. J. Quinn", "Suzanna L. Arcand", "Karen Gambaro", "Jason Madore", "Ashley H. Birch", "Manon de Ladurantaye", "Kurosh Rahimi", "Diane M. Provencher", "Anne-Marie Mes-Masson", "Celia M. T. Greenwood", "Patricia N. Tonin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0045484.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TP53_gene_expression_protein_expression_and_Kaplan_Meier_survival_curve_analyses_in_HGSC_cases_/243263", "title"=>"<i>TP53</i> gene expression, protein expression and Kaplan-Meier survival curve analyses in HGSC cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-20 00:54:23"}

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  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"11", "full-text"=>"14", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Computational biology", "average_usage"=>[375, 629, 760, 889, 1000, 1110, 1203, 1298, 1399, 1492, 1603, 1699, 1774, 1855, 1918, 1998, 2062, 2152, 2227, 2312, 2378, 2461, 2528, 2600, 2664]}]}
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