CiteULike | Further Information

• {"link"=>{"url"=>"http://www.citeulike.org/group/13922/article/13518644"}, "post_time"=>"2015-02-16 16:51:34", "tag"=>["ncg42", "sarcoma"], "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.pgen.1004475"}, "group"=>"Ciccarelli Lab", "group_id"=>"13922", "article_id"=>"13518644"}

Mendeley | Further Information

{"title"=>"The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent STAG2 Mutation", "type"=>"journal", "authors"=>[{"first_name"=>"Andrew S.", "last_name"=>"Brohl", "scopus_author_id"=>"55939305000"}, {"first_name"=>"David A.", "last_name"=>"Solomon", "scopus_author_id"=>"35312395700"}, {"first_name"=>"Wendy", "last_name"=>"Chang", "scopus_author_id"=>"26646250900"}, {"first_name"=>"Jianjun", "last_name"=>"Wang", "scopus_author_id"=>"56080539700"}, {"first_name"=>"Young", "last_name"=>"Song", "scopus_author_id"=>"7404919892"}, {"first_name"=>"Sivasish", "last_name"=>"Sindiri", "scopus_author_id"=>"34969588500"}, {"first_name"=>"Rajesh", "last_name"=>"Patidar", "scopus_author_id"=>"56369048900"}, {"first_name"=>"Laura", "last_name"=>"Hurd", "scopus_author_id"=>"55217310300"}, {"first_name"=>"Li", "last_name"=>"Chen", "scopus_author_id"=>"57192609376"}, {"first_name"=>"Jack F.", "last_name"=>"Shern", "scopus_author_id"=>"6506131884"}, {"first_name"=>"Hongling", "last_name"=>"Liao", "scopus_author_id"=>"36016901800"}, {"first_name"=>"Xinyu", "last_name"=>"Wen", "scopus_author_id"=>"35313033300"}, {"first_name"=>"Julia", "last_name"=>"Gerard", "scopus_author_id"=>"55875567700"}, {"first_name"=>"Jung Sik", "last_name"=>"Kim", "scopus_author_id"=>"8973248600"}, {"first_name"=>"Jose Antonio", "last_name"=>"Lopez Guerrero", "scopus_author_id"=>"7003503905"}, {"first_name"=>"Isidro", "last_name"=>"Machado", "scopus_author_id"=>"24470479300"}, {"first_name"=>"Daniel H.", "last_name"=>"Wai", "scopus_author_id"=>"22949215300"}, {"first_name"=>"Piero", "last_name"=>"Picci", "scopus_author_id"=>"7102271842"}, {"first_name"=>"Timothy", "last_name"=>"Triche", "scopus_author_id"=>"7004983032"}, {"first_name"=>"Andrew E.", "last_name"=>"Horvai", "scopus_author_id"=>"6505904465"}, {"first_name"=>"Markku", "last_name"=>"Miettinen", "scopus_author_id"=>"7101638419"}, {"first_name"=>"Jun S.", "last_name"=>"Wei", "scopus_author_id"=>"35281388400"}, {"first_name"=>"Daniel", "last_name"=>"Catchpool", "scopus_author_id"=>"56310372800"}, {"first_name"=>"Antonio", "last_name"=>"Llombart-Bosch", "scopus_author_id"=>"55664842500"}, {"first_name"=>"Todd", "last_name"=>"Waldman", "scopus_author_id"=>"6603946286"}, {"first_name"=>"Javed", "last_name"=>"Khan", "scopus_author_id"=>"7201898500"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84905457348", "issn"=>"15537404", "pui"=>"373701235", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "sgr"=>"84905457348", "pmid"=>"25010205", "doi"=>"10.1371/journal.pgen.1004475"}, "id"=>"ebe2161d-05b0-3077-9bdd-df0e5c4f39cf", "abstract"=>"The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared to population data (OR 7.1, p = 0.006). Using whole transcriptome sequencing, we find that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and that these tumors do not have a characteristic Ewing sarcoma gene expression signature. We identify samples harboring novel fusion genes including FUS-NCATc2 and CIC-FOXO4 that may represent distinct small round blue cell tumor variants. In an independent EFT tissue microarray cohort, we show that STAG2 loss as detected by immunohistochemistry may be associated with more advanced disease (p = 0.15) and a modest decrease in overall survival (p = 0.10). These results significantly advance our understanding of the genomic and molecular underpinnings of Ewing sarcoma and provide a foundation towards further efforts to improve diagnosis, prognosis, and precision therapeutics testing.", "link"=>"http://www.mendeley.com/research/genomic-landscape-ewing-sarcoma-family-tumors-reveals-recurrent-stag2-mutation", "reader_count"=>99, "reader_count_by_academic_status"=>{"Unspecified"=>6, "Professor > Associate Professor"=>4, "Researcher"=>27, "Student > Doctoral Student"=>6, "Student > Ph. D. 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• {"id"=>"493878518971760640", "text"=>"#PLOSGenetics: The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent STAG2 Mutation http://t.co/tcIRaJ5AOh", "created_at"=>"2014-07-28T21:59:49Z", "user"=>"jalopezg70", "user_name"=>"J. A. López-Guerrero", "user_profile_image"=>"http://pbs.twimg.com/profile_images/468337094935322625/-UwGACc-_normal.png"}
• {"id"=>"493882648419635200", "text"=>"RT @jalopezg70: #PLOSGenetics: The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent STAG2 Mutation http://t.co/tcI…", "created_at"=>"2014-07-28T22:16:13Z", "user"=>"ewingscancerNL", "user_name"=>"EwingsCancerNL", "user_profile_image"=>"http://pbs.twimg.com/profile_images/444436063566974976/C2Wq0i4i_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1588385"], "description"=>"<p>Circos plot tracks represent somatic mutations, from outside circle: mutated genes including missense (Black), indel (Red) and nonsense (Orange); genomic location; genome copy number alterations (Grey); lesser allele frequency (Green); LOH (dotted track); density of heterozygous SNPs (Orange); density of homozygous SNPs (Blue); Intrachromasomal (Grey) and interchromasomal (Red) rearrangements. Tumor EWS2006 (A) contains only 2 somatic coding mutations. Tumor EWS2017 (B) has 4 somatic coding mutations including a frameshift mutation in <i>STAG2</i>. Both tumors shown have the characteristic <i>EWSR1-FLI1</i> fusion and a modest degree of aneuploidy.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "oncology", "Cancers and neoplasms", "sarcomas", "Ewing sarcoma", "ewing", "sarcoma"], "article_id"=>1099944, "categories"=>["Biological Sciences"], "users"=>["Andrew S. Brohl", "David A. Solomon", "Wendy Chang", "Jianjun Wang", "Young Song", "Sivasish Sindiri", "Rajesh Patidar", "Laura Hurd", "Li Chen", "Jack F. Shern", "Hongling Liao", "Xinyu Wen", "Julia Gerard", "Jung-Sik Kim", "Jose Antonio Lopez Guerrero", "Isidro Machado", "Daniel H. Wai", "Piero Picci", "Timothy Triche", "Andrew E. Horvai", "Markku Miettinen", "Jun S. Wei", "Daniel Catchpool", "Antonio Llombart-Bosch", "Todd Waldman", "Javed Khan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004475.g001", "stats"=>{"downloads"=>5, "page_views"=>88, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Circos_plots_of_representative_Ewing_sarcoma_family_tumors_/1099944", "title"=>"Circos plots of representative Ewing sarcoma family tumors.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-10 03:35:23"}
• {"files"=>["https://ndownloader.figshare.com/files/1588421"], "description"=>"<p>*4 cell lines were tested only for <i>STAG2</i> mutation but not <i>TP53</i> nor <i>CDKN2A</i>.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "oncology", "Cancers and neoplasms", "sarcomas", "Ewing sarcoma", "recurrently", "altered", "genes", "ewing", "sarcoma", "tumors"], "article_id"=>1099974, "categories"=>["Biological Sciences"], "users"=>["Andrew S. Brohl", "David A. Solomon", "Wendy Chang", "Jianjun Wang", "Young Song", "Sivasish Sindiri", "Rajesh Patidar", "Laura Hurd", "Li Chen", "Jack F. Shern", "Hongling Liao", "Xinyu Wen", "Julia Gerard", "Jung-Sik Kim", "Jose Antonio Lopez Guerrero", "Isidro Machado", "Daniel H. Wai", "Piero Picci", "Timothy Triche", "Andrew E. Horvai", "Markku Miettinen", "Jun S. Wei", "Daniel Catchpool", "Antonio Llombart-Bosch", "Todd Waldman", "Javed Khan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004475.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutational_frequency_of_recurrently_altered_genes_in_Ewing_sarcoma_family_tumors_and_cell_lines_/1099974", "title"=>"Mutational frequency of recurrently altered genes in Ewing sarcoma family tumors and cell lines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-10 03:35:23"}
• {"files"=>["https://ndownloader.figshare.com/files/1588412"], "description"=>"<p>13 of 36 cell lines have complete absence of STAG2 protein, an additional two cell lines (6647 and TC-215) have STAG2 isoforms with altered molecular weight due to large intragenic in-frame insertions or deletions, one additional cell line (ES-7) has intact STAG2 expression despite a frameshift mutation occurring at amino acid residue 1212 that is C-terminal to the epitope recognized by the antibody, and two additional cell lines have intact STAG2 expression but harbor a small in-frame insertion (CHLA-9) and a missense mutation (ES-6). Absence of p16INK4a protein is seen in 25/36 cell lines including all 16 with identified <i>CDKN2A</i> deletion.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "oncology", "Cancers and neoplasms", "sarcomas", "Ewing sarcoma", "blots", "36", "eft"], "article_id"=>1099971, "categories"=>["Biological Sciences"], "users"=>["Andrew S. Brohl", "David A. Solomon", "Wendy Chang", "Jianjun Wang", "Young Song", "Sivasish Sindiri", "Rajesh Patidar", "Laura Hurd", "Li Chen", "Jack F. Shern", "Hongling Liao", "Xinyu Wen", "Julia Gerard", "Jung-Sik Kim", "Jose Antonio Lopez Guerrero", "Isidro Machado", "Daniel H. Wai", "Piero Picci", "Timothy Triche", "Andrew E. Horvai", "Markku Miettinen", "Jun S. Wei", "Daniel Catchpool", "Antonio Llombart-Bosch", "Todd Waldman", "Javed Khan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004475.g005", "stats"=>{"downloads"=>1, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_blots_analysis_of_STAG2_TP53_p21_WAF1_CIP1_and_p16_INK4a_on_a_panel_of_36_unique_EFT_cell_lines_/1099971", "title"=>"Western blots analysis of STAG2, TP53, p21^WAF1/CIP1, and p16^INK4a on a panel of 36 unique EFT cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-10 03:35:23"}
• {"files"=>["https://ndownloader.figshare.com/files/1588397"], "description"=>"<p>EFT clinical samples that lack an EWSR1-fusion have a distinct profile. A) Hierarchical clustering based on RNA expressional profile shows the fusion negative (blue) and alternate fusion (red) samples to separate from the majority of EWSR1-fusion positive EFTs. B) Expression profile of Ewing sarcoma signature genes (top) and genes correlating with EWSR1-FLI1 target <i>NROB1</i> (bottom) in normal tissues and EFT cohort demonstrating the lack of typical expressional profile in EWSR1-fusion negative samples (Alt).</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "oncology", "Cancers and neoplasms", "sarcomas", "Ewing sarcoma", "profiling", "ewing", "sarcoma", "tumors", "rna", "sequencing"], "article_id"=>1099956, "categories"=>["Biological Sciences"], "users"=>["Andrew S. Brohl", "David A. Solomon", "Wendy Chang", "Jianjun Wang", "Young Song", "Sivasish Sindiri", "Rajesh Patidar", "Laura Hurd", "Li Chen", "Jack F. Shern", "Hongling Liao", "Xinyu Wen", "Julia Gerard", "Jung-Sik Kim", "Jose Antonio Lopez Guerrero", "Isidro Machado", "Daniel H. Wai", "Piero Picci", "Timothy Triche", "Andrew E. Horvai", "Markku Miettinen", "Jun S. Wei", "Daniel Catchpool", "Antonio Llombart-Bosch", "Todd Waldman", "Javed Khan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004475.g002", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_profiling_of_Ewing_sarcoma_family_tumors_using_RNA_sequencing_data_/1099956", "title"=>"Molecular profiling of Ewing sarcoma family tumors using RNA sequencing data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-10 03:35:23"}
• {"files"=>["https://ndownloader.figshare.com/files/1588411"], "description"=>"<p>A) STAG2 is robustly expressed in EFT harboring wild-type STAG2 alleles (top), but is completely lost in the subset of EFT harboring truncating mutations of the <i>STAG2</i> gene (bottom). Expression is retained within the non-neoplastic stromal and endothelial cells, demonstrating the somatic nature of STAG2 loss in these tumors. B) Sequence trace demonstrating the E984X <i>STAG2</i> nonsense mutation present in EFT sample NCI-0047 that is shown in A.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "oncology", "Cancers and neoplasms", "sarcomas", "Ewing sarcoma", "immunohistochemistry", "stag2", "ewing", "sarcoma"], "article_id"=>1099970, "categories"=>["Biological Sciences"], "users"=>["Andrew S. Brohl", "David A. Solomon", "Wendy Chang", "Jianjun Wang", "Young Song", "Sivasish Sindiri", "Rajesh Patidar", "Laura Hurd", "Li Chen", "Jack F. Shern", "Hongling Liao", "Xinyu Wen", "Julia Gerard", "Jung-Sik Kim", "Jose Antonio Lopez Guerrero", "Isidro Machado", "Daniel H. Wai", "Piero Picci", "Timothy Triche", "Andrew E. Horvai", "Markku Miettinen", "Jun S. Wei", "Daniel Catchpool", "Antonio Llombart-Bosch", "Todd Waldman", "Javed Khan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004475.g004", "stats"=>{"downloads"=>2, "page_views"=>66, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Examples_of_immunohistochemistry_showing_STAG2_expression_in_Ewing_sarcoma_tumor_samples_/1099970", "title"=>"Examples of immunohistochemistry showing STAG2 expression in Ewing sarcoma tumor samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-10 03:35:23"}
• {"files"=>["https://ndownloader.figshare.com/files/1588430", "https://ndownloader.figshare.com/files/1588431", "https://ndownloader.figshare.com/files/1588432", "https://ndownloader.figshare.com/files/1588433", "https://ndownloader.figshare.com/files/1588434", "https://ndownloader.figshare.com/files/1588435", "https://ndownloader.figshare.com/files/1588436", "https://ndownloader.figshare.com/files/1588437", "https://ndownloader.figshare.com/files/1588438", "https://ndownloader.figshare.com/files/1588439", "https://ndownloader.figshare.com/files/1588440", "https://ndownloader.figshare.com/files/1588441", "https://ndownloader.figshare.com/files/1588442", "https://ndownloader.figshare.com/files/1588443", "https://ndownloader.figshare.com/files/1588444", "https://ndownloader.figshare.com/files/1588445", "https://ndownloader.figshare.com/files/1588446", "https://ndownloader.figshare.com/files/1588447", "https://ndownloader.figshare.com/files/1588448", "https://ndownloader.figshare.com/files/1588449", "https://ndownloader.figshare.com/files/1588451", "https://ndownloader.figshare.com/files/1588452"], "description"=>"<div><p>The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit <i>STAG2</i> (21.5% tumors, 44.4% cell lines), homozygous deletion of <i>CDKN2A</i> (13.8% and 50%) and mutations of <i>TP53</i> (6.2% and 71.9%). We additionally note an increased prevalence of the <i>BRCA2</i> K3326X polymorphism in EFT patient samples (7.3%) compared to population data (OR 7.1, p = 0.006). Using whole transcriptome sequencing, we find that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and that these tumors do not have a characteristic Ewing sarcoma gene expression signature. We identify samples harboring novel fusion genes including <i>FUS-NCATc2</i> and <i>CIC-FOXO4</i> that may represent distinct small round blue cell tumor variants. In an independent EFT tissue microarray cohort, we show that STAG2 loss as detected by immunohistochemistry may be associated with more advanced disease (p = 0.15) and a modest decrease in overall survival (p = 0.10). These results significantly advance our understanding of the genomic and molecular underpinnings of Ewing sarcoma and provide a foundation towards further efforts to improve diagnosis, prognosis, and precision therapeutics testing.</p></div>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "oncology", "Cancers and neoplasms", "sarcomas", "Ewing sarcoma", "genomic", "ewing", "sarcoma", "tumors", "reveals", "recurrent", "mutation"], "article_id"=>1099983, "categories"=>["Biological Sciences"], "users"=>["Andrew S. Brohl", "David A. Solomon", "Wendy Chang", "Jianjun Wang", "Young Song", "Sivasish Sindiri", "Rajesh Patidar", "Laura Hurd", "Li Chen", "Jack F. Shern", "Hongling Liao", "Xinyu Wen", "Julia Gerard", "Jung-Sik Kim", "Jose Antonio Lopez Guerrero", "Isidro Machado", "Daniel H. Wai", "Piero Picci", "Timothy Triche", "Andrew E. Horvai", "Markku Miettinen", "Jun S. Wei", "Daniel Catchpool", "Antonio Llombart-Bosch", "Todd Waldman", "Javed Khan"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004475.s001", "https://dx.doi.org/10.1371/journal.pgen.1004475.s002", "https://dx.doi.org/10.1371/journal.pgen.1004475.s003", "https://dx.doi.org/10.1371/journal.pgen.1004475.s004", "https://dx.doi.org/10.1371/journal.pgen.1004475.s005", "https://dx.doi.org/10.1371/journal.pgen.1004475.s006", "https://dx.doi.org/10.1371/journal.pgen.1004475.s007", "https://dx.doi.org/10.1371/journal.pgen.1004475.s008", "https://dx.doi.org/10.1371/journal.pgen.1004475.s009", "https://dx.doi.org/10.1371/journal.pgen.1004475.s010", "https://dx.doi.org/10.1371/journal.pgen.1004475.s011", "https://dx.doi.org/10.1371/journal.pgen.1004475.s012", "https://dx.doi.org/10.1371/journal.pgen.1004475.s013", "https://dx.doi.org/10.1371/journal.pgen.1004475.s014", "https://dx.doi.org/10.1371/journal.pgen.1004475.s015", "https://dx.doi.org/10.1371/journal.pgen.1004475.s016", "https://dx.doi.org/10.1371/journal.pgen.1004475.s017", "https://dx.doi.org/10.1371/journal.pgen.1004475.s018", "https://dx.doi.org/10.1371/journal.pgen.1004475.s019", "https://dx.doi.org/10.1371/journal.pgen.1004475.s020", "https://dx.doi.org/10.1371/journal.pgen.1004475.s021", "https://dx.doi.org/10.1371/journal.pgen.1004475.s022"], "stats"=>{"downloads"=>188, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Genomic_Landscape_of_the_Ewing_Sarcoma_Family_of_Tumors_Reveals_Recurrent_STAG2_Mutation/1099983", "title"=>"The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent <i>STAG2</i> Mutation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-10 03:35:23"}
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Relative Metric

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F1000Prime | Further Information

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