Oncogene Mutations, Copy Number Gains and Mutant Allele Specific Imbalance (MASI) Frequently Occur Together in Tumor Cells
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{"title"=>"Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells", "type"=>"journal", "authors"=>[{"first_name"=>"Junichi", "last_name"=>"Soh", "scopus_author_id"=>"7006815000"}, {"first_name"=>"Naoki", "last_name"=>"Okumura", "scopus_author_id"=>"12802361600"}, {"first_name"=>"William W.", "last_name"=>"Lockwood", "scopus_author_id"=>"11939640000"}, {"first_name"=>"Hiromasa", "last_name"=>"Yamamoto", "scopus_author_id"=>"25032037200"}, {"first_name"=>"Hisayuki", "last_name"=>"Shigematsu", "scopus_author_id"=>"7101906795"}, {"first_name"=>"Wei", "last_name"=>"Zhang", "scopus_author_id"=>"7409429610"}, {"first_name"=>"Raj", "last_name"=>"Chari", "scopus_author_id"=>"11939421400"}, {"first_name"=>"David S.", "last_name"=>"Shames", "scopus_author_id"=>"34573130000"}, {"first_name"=>"Ximing", "last_name"=>"Tang", "scopus_author_id"=>"7404100928"}, {"first_name"=>"Calum", "last_name"=>"MacAulay", "scopus_author_id"=>"35370099900"}, {"first_name"=>"Marileila", "last_name"=>"Varella-Garcia", "scopus_author_id"=>"7003396171"}, {"first_name"=>"Tõnu", "last_name"=>"Vooder", "scopus_author_id"=>"13808183200"}, {"first_name"=>"Ignacio I.", "last_name"=>"Wistuba", "scopus_author_id"=>"35375776900"}, {"first_name"=>"Stephen", "last_name"=>"Lam", "scopus_author_id"=>"55193690600"}, {"first_name"=>"Rolf", "last_name"=>"Brekken", "scopus_author_id"=>"6603804348"}, {"first_name"=>"Shinichi", "last_name"=>"Toyooka", "scopus_author_id"=>"7006160439"}, {"first_name"=>"John D.", "last_name"=>"Minna", "scopus_author_id"=>"35380041500"}, {"first_name"=>"Wan L.", "last_name"=>"Lam", "scopus_author_id"=>"7203021871"}, {"first_name"=>"Adi F.", "last_name"=>"Gazdar", "scopus_author_id"=>"35372587300"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"19826477", "doi"=>"10.1371/journal.pone.0007464", "sgr"=>"70449433271", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "scopus"=>"2-s2.0-70449433271", "issn"=>"19326203", "pui"=>"355609536"}, "id"=>"7a7da3b2-9b6b-3727-b011-c8f40650e3d7", "abstract"=>"BACKGROUND: Activating mutations in one allele of an oncogene (heterozygous mutations) are widely believed to be sufficient for tumorigenesis. However, mutant allele specific imbalance (MASI) has been observed in tumors and cell lines harboring mutations of oncogenes.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: We determined 1) mutational status, 2) copy number gains (CNGs) and 3) relative ratio between mutant and wild type alleles of KRAS, BRAF, PIK3CA and EGFR genes by direct sequencing and quantitative PCR assay in over 400 human tumors, cell lines, and xenografts of lung, colorectal, and pancreatic cancers. Examination of a public database indicated that homozygous mutations of five oncogenes were frequent (20%) in 833 cell lines of 12 tumor types. Our data indicated two major forms of MASI: 1) MASI with CNG, either complete or partial; and 2) MASI without CNG (uniparental disomy; UPD), due to complete loss of wild type allele. MASI was a frequent event in mutant EGFR (75%) and was due mainly to CNGs, while MASI, also frequent in mutant KRAS (58%), was mainly due to UPD. Mutant: wild type allelic ratios at the genomic level were precisely maintained after transcription. KRAS mutations or CNGs were significantly associated with increased ras GTPase activity, as measured by ELISA, and the two molecular changes were synergistic. Of 237 lung adenocarcinoma tumors, the small number with both KRAS mutation and CNG were associated with shortened survival.\\n\\nCONCLUSIONS: MASI is frequently present in mutant EGFR and KRAS tumor cells, and is associated with increased mutant allele transcription and gene activity. The frequent finding of mutations, CNGs and MASI occurring together in tumor cells indicates that these three genetic alterations, acting together, may have a greater role in the development or maintenance of the malignant phenotype than any individual alteration.", "link"=>"http://www.mendeley.com/research/oncogene-mutations-copy-number-gains-mutant-allele-specific-imbalance-masi-frequently-occur-together", "reader_count"=>96, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>8, "Librarian"=>1, "Researcher"=>37, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Other"=>6, "Student > Master"=>3, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>8, "Librarian"=>1, "Researcher"=>37, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Other"=>6, "Student > Master"=>3, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>10, "Biochemistry, Genetics and Molecular Biology"=>15, "Mathematics"=>2, "Medicine and Dentistry"=>22, "Agricultural and Biological Sciences"=>39, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>2, "Computer Science"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>22}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>39}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>15}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>10}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Belgium"=>2, "United States"=>1, "Ireland"=>1, "Japan"=>1, "United Kingdom"=>1, "France"=>2, "Switzerland"=>1, "Germany"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/880285"], "description"=>"<p>a) types of MASI. Three major types of MASI may occur. b) Complete MASI of <i>KRAS</i> gene as identified in 1991. We reported <i>KRAS</i> mutations in non-small-cell lung cancer (NSCLC) cell lines using restriction fragment length polymorphism (RFLP) method which can digest only wild type (WT) allele. We made this figure using modified methodologies from the original publication <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007464#pone.0007464-Mitsudomi1\" target=\"_blank\">[3]</a>. Three out of four <i>KRAS</i> mutant NSCLC lines showed homozygous mutations (complete MASI) of <i>KRAS</i> codon 12. NT, no treatment of restriction enzyme; +, presence of treatment of restriction enzyme. c) Our first <i>EGFR</i> mutation (exon 19 deletion) showed that the mutant allele was in great excess compared to the WT allele. WT, wild type.</p>", "links"=>[], "tags"=>["allele", "imbalance", "earlier"], "article_id"=>550720, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutant_allele_specific_imbalance_MASI_and_some_earlier_observations_/550720", "title"=>"Mutant allele specific imbalance (MASI) and some earlier observations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:12:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/880483"], "description"=>"<p>a) The association between mutations and CNG of <i>EGFR</i> pathway genes in cell lines and tumors across organs. We combined the data of cell lines and tumors because of similarity of both data sets. Mutations are more frequent than CNG in <i>KRAS</i> gene while CNG are more frequent than mutations in other genes. CNG are significantly correlated with mutations in <i>KRAS</i> (<i>P</i><0.0001) and <i>EGFR</i> (<i>P</i><0.0001) genes (*). However, mutations or CNGs of <i>BRAF</i> and <i>PIK3CA</i> genes are usually exclusive and rarely present together. b) The association between percent of mutant allele (mA%) and copy number for 75 mutations in 68 mutant cell lines. Gray dotted line is the hypothetical curve of mutant allele specific amplification. There were 36 mutations with MASI (48%), 38 with balanced (51%) and one with reverse MASI (1%). Thirteen mutant cell lines including mutant <i>KRAS</i> (n = 12) and <i>BRAF</i> (n = 1) had uniparental disomy (complete MASI without CNG) and four lines (all mutant <i>KRAS</i>) had complete MASI with modest level of CNG (copy number<9, black dotted circle). The prefix m- means mutant; mA%, proportion of mutant allele.</p>", "links"=>[], "tags"=>["mutant", "allele", "imbalance", "pathway"], "article_id"=>550919, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_association_between_mutations_copy_number_gain_CNG_and_mutant_allele_specific_imbalance_MASI_of_EGFR_pathway_genes_/550919", "title"=>"The association between mutations, copy number gain (CNG) and mutant allele specific imbalance (MASI) of <i>EGFR</i> pathway genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:15:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/881218"], "description"=>"<p>AI, allelic imbalance; MASI, mutant allele specific imbalance; WT, wild type; UPD, uniparental disomy; CNG, copy number gain.</p>", "links"=>[], "tags"=>["allelic", "imbalance", "pathway"], "article_id"=>551655, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.t002", "stats"=>{"downloads"=>6, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_allelic_imbalance_of_EGFR_pathway_genes_/551655", "title"=>"Summary of allelic imbalance of <i>EGFR</i> pathway genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-10-14 00:27:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/880383"], "description"=>"<p>Quantitation of mutant allele (mA) by direct sequencing (a and b). wA, wild type allele; WT, wild type; mA%, proportion of mutant allele. a) Calculation method of mA% in point mutations by sequencing eletcropherogram is shown. b) An example of accuracy of mutant allelic quantitation (mA%) by measurement of sequencing electropherogram (<i>KRAS</i> mutation: G12V, 35GKRAS, <i>BRAF</i>, <i>PIK3CA</i> or <i>EGFR</i> genes and confirmed the accuracy of mA% by measurement of sequencing electropherograms. F, forward sequencing; R, reverse sequencing c) and d) Frequency of homozygous mutations of 11 well-described tumor related genes in 833 cancer cell lines collected at Cancer Genome Project, Welcome Trust Sanger Institute (<a href=\"http://www.sanger.ac.uk/\" target=\"_blank\">www.sanger.ac.uk/</a>). As expected, homozygous mutations are frequent in six tumor suppressor genes (c). Those of five oncogenes are also relatively frequent (d). MASI, mutant allele specific imbalance; The prefix m- means mutant.</p>", "links"=>[], "tags"=>["mutations", "oncogenes"], "article_id"=>550818, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Homozygous_mutations_complete_MASI_of_oncogenes_are_frequent_/550818", "title"=>"Homozygous mutations (complete MASI) of oncogenes are frequent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:13:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/880842"], "description"=>"<p>Gene dosage is highly associated with mRNA expression level (a). Proportion of mutant allele (mA%) determined by DNA sequencing electropherogram is significantly consistent with mA% by cDNA sequencing using different sets of primers (b). c) <i>KRAS</i> alterations are related to ras GTPase activity. <i>KRAS</i> mutations or copy number gains (CNGs) alone are related to high ras GTPase activity and the two molecular changes are synergistic. The prefix m- means mutant. HBEC, human bronchial epithelial cell; WT, wild type; UPD, uniparental disomy; *, <i>KRAS</i> mutation with CNG versus Others; **, <i>KRAS</i> mutation with CNG versus either <i>KRAS</i> mutation or CNG; ***, either <i>KRAS</i> mutation or CNG versus WT.</p>", "links"=>[], "tags"=>["mutant", "allele", "imbalance"], "article_id"=>551279, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g006", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Biological_role_of_mutant_allele_specific_imbalance_MASI_/551279", "title"=>"Biological role of mutant allele specific imbalance (MASI).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:21:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/436306", "https://ndownloader.figshare.com/files/436322", "https://ndownloader.figshare.com/files/436342", "https://ndownloader.figshare.com/files/436360", "https://ndownloader.figshare.com/files/436369", "https://ndownloader.figshare.com/files/436382", "https://ndownloader.figshare.com/files/436408", "https://ndownloader.figshare.com/files/436419", "https://ndownloader.figshare.com/files/436463", "https://ndownloader.figshare.com/files/436524", "https://ndownloader.figshare.com/files/436589"], "description"=>"<div><h3>Background</h3><p>Activating mutations in one allele of an oncogene (heterozygous mutations) are widely believed to be sufficient for tumorigenesis. However, mutant allele specific imbalance (MASI) has been observed in tumors and cell lines harboring mutations of oncogenes.</p><h3>Methodology/Principal Findings</h3><p>We determined 1) mutational status, 2) copy number gains (CNGs) and 3) relative ratio between mutant and wild type alleles of <em>KRAS</em>, <em>BRAF</em>, <em>PIK3CA</em> and <em>EGFR</em> genes by direct sequencing and quantitative PCR assay in over 400 human tumors, cell lines, and xenografts of lung, colorectal, and pancreatic cancers. Examination of a public database indicated that homozygous mutations of five oncogenes were frequent (20%) in 833 cell lines of 12 tumor types. Our data indicated two major forms of MASI: 1) MASI with CNG, either complete or partial; and 2) MASI without CNG (uniparental disomy; UPD), due to complete loss of wild type allele. MASI was a frequent event in mutant <em>EGFR</em> (75%) and was due mainly to CNGs, while MASI, also frequent in mutant <em>KRAS</em> (58%), was mainly due to UPD. Mutant: wild type allelic ratios at the genomic level were precisely maintained after transcription. <em>KRAS</em> mutations or CNGs were significantly associated with increased ras GTPase activity, as measured by ELISA, and the two molecular changes were synergistic. Of 237 lung adenocarcinoma tumors, the small number with both <em>KRAS</em> mutation and CNG were associated with shortened survival.</p><h3>Conclusions</h3><p>MASI is frequently present in mutant <em>EGFR</em> and <em>KRAS</em> tumor cells, and is associated with increased mutant allele transcription and gene activity. The frequent finding of mutations, CNGs and MASI occurring together in tumor cells indicates that these three genetic alterations, acting together, may have a greater role in the development or maintenance of the malignant phenotype than any individual alteration.</p></div>", "links"=>[], "tags"=>["oncogene", "gains", "mutant", "allele", "imbalance", "cells"], "article_id"=>146032, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0007464.s001", "https://dx.doi.org/10.1371/journal.pone.0007464.s002", "https://dx.doi.org/10.1371/journal.pone.0007464.s003", "https://dx.doi.org/10.1371/journal.pone.0007464.s004", "https://dx.doi.org/10.1371/journal.pone.0007464.s005", "https://dx.doi.org/10.1371/journal.pone.0007464.s006", "https://dx.doi.org/10.1371/journal.pone.0007464.s007", "https://dx.doi.org/10.1371/journal.pone.0007464.s008", "https://dx.doi.org/10.1371/journal.pone.0007464.s009", "https://dx.doi.org/10.1371/journal.pone.0007464.s010", "https://dx.doi.org/10.1371/journal.pone.0007464.s011"], "stats"=>{"downloads"=>48, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Oncogene_Mutations_Copy_Number_Gains_and_Mutant_Allele_Specific_Imbalance_MASI_Frequently_Occur_Together_in_Tumor_Cells/146032", "title"=>"Oncogene Mutations, Copy Number Gains and Mutant Allele Specific Imbalance (MASI) Frequently Occur Together in Tumor Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-10-14 01:40:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/881111"], "description"=>"*<p>, Zygosity status was determined by manual examination of sequencing electropherograms at Sanger institute; **, Homozygous mutations were defined as percent of mutant allele by direct sequencing greater than 90%.</p>", "links"=>[], "tags"=>["mutations", "oncogenes", "cancer"], "article_id"=>551549, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.t001", "stats"=>{"downloads"=>6, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Homozygous_mutations_of_oncogenes_are_frequent_in_cancer_cell_lines_/551549", "title"=>"Homozygous mutations of oncogenes are frequent in cancer cell lines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-10-14 00:25:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/880591"], "description"=>"<p>(Left upper) Copy number and allelic imbalance status as determined by SNP 6.0 arrays are depicted for representative cell lines with balanced and MASI patterns of <i>KRAS</i> mutant/wild type allele ratios. For copy number, each blue dot represents an array element ordered by genomic position. Those shifted to the left of the middle line have decreased copy number whereas those shifted to the right have increased copy number. For allelic imbalance, dashed lines represent regions with no imbalance whereas solid lines represent those with imbalance. Thicker solid lines represent the region of maximum imbalance across the chromosome arm (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007464#s2\" target=\"_blank\">methods</a>). The genomic location of <i>KRAS</i> is indicated by the horizontal black line. (Left lower) Electropherograms of direct DNA sequencing with mutant allele proportion (mA%, determined by electropherogram) and <i>KRAS</i> copy number (copy#, determined by quantitative PCR) are present in the same cell lines used for SNP arrays. (Right lower) <i>KRAS</i> FISH in HCC1171 was performed using purified DNA from BAC clone RP11-1119I8 encompassing the <i>KRAS</i> gene (red signal) and CEP12-SpectrumGreen (Abbott Molecular, IL) as an internal control. Means of <i>KRAS</i> copy number are 21.6±11.0 (standard deviation, SD) and those of CEP12 number are 3.7±1.2 (SD). Both SNP arrays and gene specific assays confirm that HCC2347 displays neutral <i>KRAS</i> copy number with no imbalance (mutant/wild type balanced) whereas HCC1171 and H2030 display imbalance (MASI) with copy number gain (CNG) or uniparental disomy (UPD), respectively.</p>", "links"=>[], "tags"=>["mutant", "allele", "imbalance", "cancer"], "article_id"=>551023, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_KRAS_mutant_allele_specific_imbalance_MASI_in_lung_cancer_cell_lines_/551023", "title"=>"<i>KRAS</i> mutant allele specific imbalance (MASI) in lung cancer cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:17:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/881011"], "description"=>"<p>The effect of 1) <i>KRAS</i> mutations (without CNG), 2) <i>KRAS</i> CNG (without mutations), 3) both <i>KRAS</i> mutations and CNG, and 4) others (without <i>KRAS</i> mutations and CNGs) on clinical outcome is shown. Tumors having both alterations indicate worse prognosis with borderline significance than all others (<i>P</i> = 0.04). The prefix m- means mutant.</p>", "links"=>[], "tags"=>["mutations", "237"], "article_id"=>551448, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g007", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_KRAS_mutations_and_copy_number_gain_CNG_on_clinical_outcome_in_237_lung_adenocarcinomas_/551448", "title"=>"The effect of <i>KRAS</i> mutations and copy number gain (CNG) on clinical outcome in 237 lung adenocarcinomas.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:24:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/881170"], "description"=>"<p>Mut, mutation; WT, wild type; CNG, copy number gain; NS, not significant; *, Smoking status was not available in three cases; **, Nineteen cases were not determined mutational status and copy number of <i>EGFR</i> gene.</p>", "links"=>[], "tags"=>["alterations", "factors", "288"], "article_id"=>551606, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.t003", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_association_between_KRAS_alterations_and_clinical_and_other_genetic_factors_in_288_lung_adenocarcinomas_/551606", "title"=>"The association between <i>KRAS</i> alterations and clinical and other genetic factors in 288 lung adenocarcinomas.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-10-14 00:26:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/880753"], "description"=>"<p>MASI is equally frequent in mutant <i>KRAS</i> and <i>EGFR</i> genes than others and <i>PIK3CA</i> MASI is rare (a). <i>KRAS</i> MASI is caused almost equally by uniparental disomy or copy number gain (CNG) while <i>EGFR</i> MASI is mainly caused by CNG (b). The prefix m- means mutant. MASI, mutant allele specific imbalance.</p>", "links"=>[], "tags"=>["frequencies", "mechanisms", "masi", "pathway"], "article_id"=>551183, "categories"=>["Cancer", "Genetics", "Molecular Biology"], "users"=>["Junichi Soh", "Naoki Okumura", "William W. Lockwood", "Hiromasa Yamamoto", "Hisayuki Shigematsu", "Wei Zhang", "Raj Chari", "David S. Shames", "Ximing Tang", "Calum MacAulay", "Marileila Varella-Garcia", "Tõnu Vooder", "Ignacio I. Wistuba", "Stephen Lam", "Rolf Brekken", "Shinichi Toyooka", "John D. Minna", "Wan L. Lam", "Adi F. Gazdar"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007464.g005", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Different_frequencies_and_mechanisms_of_MASI_of_EGFR_pathway_genes_/551183", "title"=>"Different frequencies and mechanisms of MASI of <i>EGFR</i> pathway genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-10-14 00:19:43"}

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Relative Metric

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