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{"title"=>"Rare copy number variants observed in hereditary breast cancer cases disrupt genes in estrogen signaling and TP53 tumor suppression network", "type"=>"journal", "authors"=>[{"first_name"=>"Katri", "last_name"=>"Pylkäs", "scopus_author_id"=>"57200806362"}, {"first_name"=>"Mikko", "last_name"=>"Vuorela", "scopus_author_id"=>"37078347200"}, {"first_name"=>"Meeri", "last_name"=>"Otsukka", "scopus_author_id"=>"55317905500"}, {"first_name"=>"Anne", "last_name"=>"Kallioniemi", "scopus_author_id"=>"7004959670"}, {"first_name"=>"Arja", "last_name"=>"Jukkola-Vuorinen", "scopus_author_id"=>"12767449500"}, {"first_name"=>"Robert", "last_name"=>"Winqvist", "scopus_author_id"=>"7004554012"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"22737080", "doi"=>"10.1371/journal.pgen.1002734", "sgr"=>"84864040193", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "scopus"=>"2-s2.0-84864040193", "issn"=>"15537390", "pui"=>"365284218"}, "id"=>"08b7c5b9-951a-3575-a74f-bdec2accd27d", "abstract"=>"Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number variants (CNVs) in breast cancer predisposition, high-resolution genome-wide scans were performed on genomic DNA of 103 BRCA1, BRCA2, and PALB2 mutation negative familial breast cancer cases and 128 geographically matched healthy female controls; for replication an independent cohort of 75 similarly mutation negative young breast cancer patients was used. All observed rare variants were confirmed by independent methods. The studied breast cancer cases showed a consistent increase in the frequency of rare CNVs when compared to controls. Furthermore, the biological networks of the disrupted genes differed between the two groups. In familial cases the observed mutations disrupted genes, which were significantly overrepresented in cellular functions related to maintenance of genomic integrity, including DNA double-strand break repair (P = 0.0211). Biological network analysis in the two independent breast cancer cohorts showed that the disrupted genes were closely related to estrogen signaling and TP53 centered tumor suppressor network. These results suggest that rare CNVs represent an alternative source of genetic variation influencing hereditary risk for breast cancer.", "link"=>"http://www.mendeley.com/research/rare-copy-number-variants-observed-hereditary-breast-cancer-cases-disrupt-genes-estrogen-signaling-t", "reader_count"=>34, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>4, "Physics and Astronomy"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Canada"=>1, "Hong Kong"=>1, "United States"=>1, "United Kingdom"=>1}, "group_count"=>2}

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• http://doi.org/10.1371/journal.pone.0098653
• http://doi.org/10.1111/cge.12447
• http://doi.org/10.1016/j.mgene.2015.12.005
• http://doi.org/10.1007/s00109-017-1507-7
• http://doi.org/10.1038/s41598-017-14799-7
• http://doi.org/10.1371/journal.pone.0071802
• http://doi.org/10.1002/ijc.29215
• http://doi.org/10.1007/s13258-015-0281-6
• http://doi.org/10.1186/1471-2407-14-902
• http://doi.org/10.1186/s13058-017-0825-6
• http://doi.org/10.1371/journal.pgen.1005816
• http://doi.org/10.1007/s10549-017-4388-0
• http://doi.org/10.3390/microarrays4030407
• http://doi.org/10.1093/nar/gku345
• http://doi.org/10.1186/1897-4287-11-12
• http://doi.org/10.1016/j.jid.2016.07.023
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• http://doi.org/10.1007/s00439-014-1507-4
• http://doi.org/10.1016/j.ymeth.2015.04.018

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• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosgenetics%2Farticle%3Fid%3D10.1371%252Fjournal.pgen.1002734", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

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• {"id"=>"215915371692175360", "text"=>"PLoSGenetics: Rare Copy Number Variants Observed in Hereditary Breast Cancer Cases Disrupt Genes in Estrogen Sig... http://t.co/AlbDSAzE", "created_at"=>"2012-06-21T21:13:30Z", "user"=>"genomigence", "user_name"=>"genomigence", "user_profile_image"=>"http://a0.twimg.com/profile_images/570906209/tree_normal.png"}
• {"id"=>"216144776465096705", "text"=>"Interesting article looking at prevalence of rare CNVs in BRCA mutation-negative breast families: http://t.co/T721ZYSM", "created_at"=>"2012-06-22T12:25:05Z", "user"=>"MarkRobsonMD", "user_name"=>"Mark Robson", "user_profile_image"=>"http://a0.twimg.com/profile_images/75848426/2008headshot_3cropped_normal.jpg"}
• {"id"=>"216154528620359680", "text"=>"RT @MarkRobsonMD: Interesting article looking at prevalence of rare CNVs in BRCA mutation-negative breast families: http://t.co/kVvpRCZk", "created_at"=>"2012-06-22T13:03:50Z", "user"=>"alexgoglia", "user_name"=>"Alex Goglia", "user_profile_image"=>"http://a0.twimg.com/profile_images/1763804937/IMG_3727_normal.JPG"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/619810"], "description"=>"<p>BC = breast cancer.</p>a<p>Observed only in cancer cases, or only in controls.</p>b<p>The genomic loci has annotated genes.</p>c<p>Gene disruptions include rare CNVs having breakpoints within the genes or promoter regions, and rare CNVs which delete the involved genes entirely.</p>", "links"=>[], "tags"=>["cnvs", "cancer", "cases"], "article_id"=>290304, "categories"=>["Cancer", "Biological Sciences", "Genetics", "Biotechnology"], "users"=>["Katri Pylkäs", "Mikko Vuorela", "Meeri Otsukka", "Anne Kallioniemi", "Arja Jukkola-Vuorinen", "Robert Winqvist"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002734.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proportion_of_rare_CNVs_in_breast_cancer_cases_and_controls_/290304", "title"=>"Proportion of rare CNVs in breast cancer cases and controls.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-21 00:05:04"}
• {"files"=>["https://ndownloader.figshare.com/files/619853"], "description"=>"<p>Disruption = the gene is disrupted by the CNV breakpoints; deletion = the entire gene is deleted. del = partial gene deletion; dup = partial gene duplication.</p>a<p>Based on human genome assembly 19 (February 2009).</p>b<p>Although detailed effects of partial gene duplication to gene transcription are not clear, duplication have potential to disrupt transcription by several mechanisms, such as transcriptional read-through. This can occur by tandem duplication, where gene silencing can be induced by a partially duplicated (3′ deleted) version of the gene itself <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002734#pgen.1002734-Kuiper1\" target=\"_blank\">[54]</a>.</p>", "links"=>[], "tags"=>["disrupted", "deleted", "cancer", "cases", "centered"], "article_id"=>290336, "categories"=>["Cancer", "Biological Sciences", "Genetics", "Biotechnology"], "users"=>["Katri Pylkäs", "Mikko Vuorela", "Meeri Otsukka", "Anne Kallioniemi", "Arja Jukkola-Vuorinen", "Robert Winqvist"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002734.t003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_disrupted_or_deleted_entirely_in_breast_cancer_cases_and_involved_in_TP53_and_estradiol_centered_network_/290336", "title"=>"Genes disrupted or deleted entirely in breast cancer cases and involved in <i>TP53</i> and β-estradiol centered network.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-21 00:05:36"}
• {"files"=>["https://ndownloader.figshare.com/files/619713"], "description"=>"<p>IPA was used to identify the connection between the genes disrupted in all cases (both familial and the cohort consisting of young breast cancer patients). The analysis identified two networks with (A) <i>TP53</i>, β-estradiol and <i>CTNNB1</i> (in green) occupying the central positions, and (B) β-estradiol (in green) occupying the central position. Genes disrupted in breast cancer cases are coloured with red. Solid lines indicate direct molecular interaction and dashed lines indicate indirect molecular interaction.</p>", "links"=>[], "tags"=>["dysfunction", "centered", "studied", "cancer"], "article_id"=>290202, "categories"=>["Cancer", "Biological Sciences", "Genetics", "Biotechnology"], "users"=>["Katri Pylkäs", "Mikko Vuorela", "Meeri Otsukka", "Anne Kallioniemi", "Arja Jukkola-Vuorinen", "Robert Winqvist"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002734.g001", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Indication_of_dysfunction_of_TP53_and_estradiol_centered_network_in_the_studied_breast_cancer_cases_/290202", "title"=>"Indication of dysfunction of <i>TP53</i> and β-estradiol centered network in the studied breast cancer cases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-06-21 00:03:22"}
• {"files"=>["https://ndownloader.figshare.com/files/322266", "https://ndownloader.figshare.com/files/322301", "https://ndownloader.figshare.com/files/322331", "https://ndownloader.figshare.com/files/322409", "https://ndownloader.figshare.com/files/322457"], "description"=>"<div><p>Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number variants (CNVs) in breast cancer predisposition, high-resolution genome-wide scans were performed on genomic DNA of 103 <em>BRCA1</em>, <em>BRCA2</em>, and <em>PALB2</em> mutation negative familial breast cancer cases and 128 geographically matched healthy female controls; for replication an independent cohort of 75 similarly mutation negative young breast cancer patients was used. All observed rare variants were confirmed by independent methods. The studied breast cancer cases showed a consistent increase in the frequency of rare CNVs when compared to controls. Furthermore, the biological networks of the disrupted genes differed between the two groups. In familial cases the observed mutations disrupted genes, which were significantly overrepresented in cellular functions related to maintenance of genomic integrity, including DNA double-strand break repair (<em>P</em> = 0.0211). Biological network analysis in the two independent breast cancer cohorts showed that the disrupted genes were closely related to estrogen signaling and <em>TP53</em> centered tumor suppressor network. These results suggest that rare CNVs represent an alternative source of genetic variation influencing hereditary risk for breast cancer.</p> </div>", "links"=>[], "tags"=>["variants", "observed", "hereditary", "cancer", "cases", "disrupt", "genes", "estrogen", "signaling", "suppression"], "article_id"=>123604, "categories"=>["Cancer", "Biological Sciences", "Genetics", "Biotechnology"], "users"=>["Katri Pylkäs", "Mikko Vuorela", "Meeri Otsukka", "Anne Kallioniemi", "Arja Jukkola-Vuorinen", "Robert Winqvist"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002734.s001", "https://dx.doi.org/10.1371/journal.pgen.1002734.s002", "https://dx.doi.org/10.1371/journal.pgen.1002734.s003", "https://dx.doi.org/10.1371/journal.pgen.1002734.s004", "https://dx.doi.org/10.1371/journal.pgen.1002734.s005"], "stats"=>{"downloads"=>43, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Rare_Copy_Number_Variants_Observed_in_Hereditary_Breast_Cancer_Cases_Disrupt_Genes_in_Estrogen_Signaling_and_TP53_Tumor_Suppression_Network/123604", "title"=>"Rare Copy Number Variants Observed in Hereditary Breast Cancer Cases Disrupt Genes in Estrogen Signaling and <em>TP53</em> Tumor Suppression Network", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-06-21 01:00:04"}
• {"files"=>["https://ndownloader.figshare.com/files/619892"], "description"=>"<p>No particular functions were overrepresented among controls.</p>a<p>Statistically significant false discovery rate (FDR) adjusted <i>P</i>-values; correction for multiple testing was done using the Benjamini-Hochberg method.</p>", "links"=>[], "tags"=>["cellular", "diseases", "disorders", "overrepresented", "genes", "disrupted", "familial", "cancer"], "article_id"=>290375, "categories"=>["Cancer", "Biological Sciences", "Genetics", "Biotechnology"], "users"=>["Katri Pylkäs", "Mikko Vuorela", "Meeri Otsukka", "Anne Kallioniemi", "Arja Jukkola-Vuorinen", "Robert Winqvist"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002734.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_and_cellular_functions_and_diseases_and_disorders_overrepresented_among_the_genes_disrupted_in_familial_breast_cancer_cases_/290375", "title"=>"Molecular and cellular functions, and diseases and disorders overrepresented among the genes disrupted in familial breast cancer cases.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-06-21 00:06:15"}

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Relative Metric

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F1000Prime