DNA Methylation Profiling across the Spectrum of HPV-Associated Anal Squamous Neoplasia
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{"title"=>"DNA Methylation Profiling across the Spectrum of HPV-Associated Anal Squamous Neoplasia", "type"=>"journal", "authors"=>[{"first_name"=>"Jonathan M.", "last_name"=>"Hernandez", "scopus_author_id"=>"16202501800"}, {"first_name"=>"Erin M.", "last_name"=>"Siegel", "scopus_author_id"=>"35741858800"}, {"first_name"=>"Bridget", "last_name"=>"Riggs", "scopus_author_id"=>"54412832300"}, {"first_name"=>"Steven", "last_name"=>"Eschrich", "scopus_author_id"=>"6602433990"}, {"first_name"=>"Abul", "last_name"=>"Elahi", "scopus_author_id"=>"6701924165"}, {"first_name"=>"Xiaotao", "last_name"=>"Qu", "scopus_author_id"=>"34880914300"}, {"first_name"=>"Abidemi", "last_name"=>"Ajidahun", "scopus_author_id"=>"35338923700"}, {"first_name"=>"Anders", "last_name"=>"Berglund", "scopus_author_id"=>"7006543113"}, {"first_name"=>"Domenico", "last_name"=>"Coppola", "scopus_author_id"=>"7005933277"}, {"first_name"=>"William M.", "last_name"=>"Grady", "scopus_author_id"=>"35285636500"}, {"first_name"=>"Anna R.", "last_name"=>"Giuliano", "scopus_author_id"=>"7101806090"}, {"first_name"=>"David", "last_name"=>"Shibata", "scopus_author_id"=>"7102096847"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23226306", "sgr"=>"84870589111", "doi"=>"10.1371/journal.pone.0050533", "scopus"=>"2-s2.0-84870589111", "pui"=>"366207334", "issn"=>"19326203"}, "id"=>"a8a7e303-294e-3ac0-9fe4-5b51ab620863", "abstract"=>"BACKGROUND: Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n = 3), SCC-in situ (SCC-IS; n = 11) and invasive SCC (n = 15). Thirteen women and 11 men with a median age of 44 years (range 26-81) were included in the study. Using the SFP(10) LiPA HPV-typing system, HPV was detected in at least one tissue from all patients with 93% (27/29) being positive for high-risk HPV types and 14 (93%) of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01). The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation \"hotspots\" and viral integration sites.\\n\\nCONCLUSIONS: We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies.", "link"=>"http://www.mendeley.com/research/dna-methylation-profiling-across-spectrum-hpvassociated-anal-squamous-neoplasia", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>3, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>3, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>6, "Computer Science"=>1, "Energy"=>1, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>1}, "Energy"=>{"Energy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/532461"], "description"=>"<p>Primers for Bisulfite Sequencing,</p>", "links"=>[], "tags"=>["bisulfite"], "article_id"=>202946, "categories"=>["Cancer", "Medicine", "Developmental Biology", "Infectious Diseases"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050533.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primers_for_Bisulfite_Sequencing_/202946", "title"=>"Primers for Bisulfite Sequencing,", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-30 00:49:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/532362"], "description"=>"*<p>A total of 38 HPV infections were detected in 29 tissues, due to multiple infections<b>.</b></p>", "links"=>[], "tags"=>["genotyping", "anal", "prevalence"], "article_id"=>202843, "categories"=>["Cancer", "Medicine", "Developmental Biology", "Infectious Diseases"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050533.t002", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HPV_Genotyping_of_Anal_Tissues_Overall_Prevalence_and_Across_the_Spectrum_of_Anal_Neoplasia_/202843", "title"=>"HPV Genotyping of Anal Tissues: Overall Prevalence and Across the Spectrum of Anal Neoplasia.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-30 00:47:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/288424", "https://ndownloader.figshare.com/files/288558"], "description"=>"<div><h3>Background</h3><p>Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia.</p> <h3>Methodology/Principal Findings</h3><p>Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n = 3), SCC-<em>in situ</em> (SCC-IS; n = 11) and invasive SCC (n = 15). Thirteen women and 11 men with a median age of 44 years (range 26–81) were included in the study. Using the <em>SFP<sub>10</sub> LiPA HPV-typing system</em>, HPV was detected in at least one tissue from all patients with 93% (27/29) being positive for high-risk HPV types and 14 (93%) of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01). The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation “hotspots” and viral integration sites.</p> <h3>Conclusions</h3><p>We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies.</p> </div>", "links"=>[], "tags"=>["dna", "methylation", "profiling", "hpv-associated", "anal", "squamous", "neoplasia"], "article_id"=>116807, "categories"=>["Cancer", "Medicine", "Developmental Biology"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0050533.s001", "https://dx.doi.org/10.1371/journal.pone.0050533.s002"], "stats"=>{"downloads"=>13, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/DNA_Methylation_Profiling_across_the_Spectrum_of_HPV_Associated_Anal_Squamous_Neoplasia__/116807", "title"=>"DNA Methylation Profiling across the Spectrum of HPV-Associated Anal Squamous Neoplasia", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-11-30 01:53:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/532501"], "description"=>"<p>Chromosomal Mapping of Genes with Differentially Methylated CpG Loci.</p>", "links"=>[], "tags"=>["genes", "differentially", "methylated", "cpg"], "article_id"=>202984, "categories"=>["Cancer", "Medicine", "Developmental Biology", "Infectious Diseases"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050533.t004", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chromosomal_Mapping_of_Genes_with_Differentially_Methylated_CpG_Loci_/202984", "title"=>"Chromosomal Mapping of Genes with Differentially Methylated CpG Loci.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-30 00:49:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/532225"], "description"=>"<p>Boxplots illustrating methylation levels of selected significant differentially methylated CpG sites (Mann-Whitney p<0.01) across histologic subtypes (normal and SCC-IS vs. invasive CC). Three patterns are identified: A: Loci with low methylation levels (median beta value <0.3) across all tissues. B: Loci with high methylation levels (median beta value ≥0.3) across all tissues. C: Loci demonstrating little to no methylation in non-invasive tissues with significant levels of methylation in invasive SCC.</p>", "links"=>[], "tags"=>["representations", "differentially", "methylated", "cpg"], "article_id"=>202711, "categories"=>["Cancer", "Medicine", "Developmental Biology", "Infectious Diseases"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050533.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplot_Representations_of_Selected_Differentially_Methylated_CpG_Loci_/202711", "title"=>"Boxplot Representations of Selected Differentially Methylated CpG Loci.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 00:45:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/532413"], "description"=>"*<p>CpG locus label within the GoldenGate methylation array.</p>†<p>Mann-Whitney test for methylation differences between two groups (pre-invasive vs. invasive SCC) using a conservative threshold to partially correct for multiple testing problems (p<0.01).</p>‡<p>Kruskal-Wallis non-parametric test performed to test three levels (Normal, <i>SCC-IS</i> and Invasive).</p>", "links"=>[], "tags"=>["differentially", "methylated", "cpg", "loci", "progression", "anal"], "article_id"=>202892, "categories"=>["Cancer", "Medicine", "Developmental Biology", "Infectious Diseases"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050533.t003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_with_Differentially_Methylated_CpG_Loci_in_the_Progression_of_Anal_Neoplasia_/202892", "title"=>"Genes with Differentially Methylated CpG Loci in the Progression of Anal Neoplasia.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-30 00:48:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/532091"], "description"=>"<p>DNA methylation is involved in the transcriptional activation of genes on one of the two X chromosomes in female somatic cells. In general, male and female cases clustered together with methylation levels of the majority of X-linked genes correlating well with the gender of the tissue source (i.e. little-to-no methylation in male samples and hemi-methylation in female samples). Sample gender is represented above the heatmap (pink = female, blue = male). Methylation is represented by the beta value, or percent of total signal with green representing low methylation and red representing hemi-methylation. 51 of 84 loci within X-linked genes were differentially methylated (p<0.05) between males and females.</p>", "links"=>[], "tags"=>["heatmap", "x-linked", "cpg"], "article_id"=>202573, "categories"=>["Cancer", "Medicine", "Developmental Biology", "Infectious Diseases"], "users"=>["Jonathan M. Hernandez", "Erin M. Siegel", "Bridget Riggs", "Steven Eschrich", "Abul Elahi", "Xiaotao Qu", "Abidemi Ajidahun", "Anders Berglund", "Domenico Coppola", "William M. Grady", "Anna R. Giuliano", "David Shibata"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050533.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gender_Heatmap_of_X_linked_CpG_Loci_/202573", "title"=>"Gender Heatmap of X-linked CpG Loci.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 00:42:53"}

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Relative Metric

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