Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy
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{"title"=>"Genetic analysis of T cell lymphomas in carbon ion-irradiated mice reveals frequent interstitial chromosome deletions: Implications for second cancer induction in normal tissues during carbon ion radiotherapy", "type"=>"journal", "authors"=>[{"first_name"=>"Benjamin J.", "last_name"=>"Blyth", "scopus_author_id"=>"15052948800"}, {"first_name"=>"Shizuko", "last_name"=>"Kakinuma", "scopus_author_id"=>"7004218433"}, {"first_name"=>"Masaaki", "last_name"=>"Sunaoshi", "scopus_author_id"=>"56703357500"}, {"first_name"=>"Yoshiko", "last_name"=>"Amasaki", "scopus_author_id"=>"8658177400"}, {"first_name"=>"Shinobu", "last_name"=>"Hirano-Sakairi", "scopus_author_id"=>"56703344700"}, {"first_name"=>"Kanae", "last_name"=>"Ogawa", "scopus_author_id"=>"56763236200"}, {"first_name"=>"Ayana", "last_name"=>"Shirakami", "scopus_author_id"=>"56763995000"}, {"first_name"=>"Yi", "last_name"=>"Shang", "scopus_author_id"=>"25958414500"}, {"first_name"=>"Chizuru", "last_name"=>"Tsuruoka", "scopus_author_id"=>"8440341300"}, {"first_name"=>"Mayumi", "last_name"=>"Nishimura", "scopus_author_id"=>"7403651081"}, {"first_name"=>"Yoshiya", "last_name"=>"Shimada", "scopus_author_id"=>"7402123768"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"26125582", "pui"=>"605481012", "scopus"=>"2-s2.0-84938614579", "doi"=>"10.1371/journal.pone.0130666", "sgr"=>"84938614579"}, "id"=>"49eb02e8-0529-3f9c-8e49-279fde072dc8", "abstract"=>"Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV x mum(-1)) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of 137Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikzf1, Pten, Trp53 and Bcl11b genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.", "link"=>"http://www.mendeley.com/research/genetic-analysis-t-cell-lymphomas-carbon-ionirradiated-mice-reveals-frequent-interstitial-chromosome", "reader_count"=>7, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2156341"], "description"=>"<p>The Kaplan-Meier estimator is plotted for the five irradiation groups with censored cases (causes of death other than TL) marked with crosses. Curves sharing the same letter designation (a, b or c) are not significantly different by pairwise log-rank tests (<i>P</i> > 0.05).</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468909, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.g001", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_Cell_Lymphoma_Free_Survival_of_Mice_Irradiated_with_Gamma_Rays_or_Carbon_Ions_/1468909", "title"=>"T Cell Lymphoma-Free Survival of Mice Irradiated with Gamma Rays or Carbon Ions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156342"], "description"=>"<p>The number of large interstitial deletions (>250 kb) per tumour is shown for each treatment group as a percentage of the number of tumours examined by array CGH (<i>n</i> = 4–6 per carbon group, <i>n</i> = 12 gamma group). The number of tumours analysed per carbon dose group did not permit pairwise comparisons of rank, but the difference between the pooled carbon group (<i>n</i> = 20) and the gamma group approaches significance (<i>P</i> = 0.053, Mann-Whitney U-Test). Across the four carbon groups the number of TL with at least one large interstitial deletion ranged from 50–75%, while only 25% of G-TL harboured one or more large interstitial deletions (mean of 1.4 large interstitial deletions per C-TL, and 0.5 per G-TL). Interestingly, the single G-TL with 4 large interstitial deletions contained two independent large deletions overlapping over the B cell differentiation gene <i>Pax5</i> (the only TL to have <i>Pax5</i> involvement) and was the only TL to have a rearranged immunoglobulin light chain gene, which together may point towards a distinct tumour phenotype.</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468910, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.g002", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_large_interstitial_deletion_frequency_by_irradiation_group_/1468910", "title"=>"Distribution of large interstitial deletion frequency by irradiation group.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156343"], "description"=>"<p>Data for chromosomes 11, 12 and 19, from twelve G-TL and twenty C-TL are shown. Each column represents a single tumour down through all three panels. Columns are ordered manually based on observed groupings. Each row represents either LOH and DNA copy number (CGH) data, DNA copy number data only (<i>Bcl11b</i> locus) or DNA copy number and mutation data (<i>Ikzf1</i>, <i>Trp53</i> and <i>Pten</i> loci). Locations noted in each row are from GRCm38 positioning.</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468911, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.g003", "stats"=>{"downloads"=>2, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Combined_DNA_copy_number_information_loss_or_retention_of_heterozygosity_and_mutation_screening_/1468911", "title"=>"Combined DNA copy number information, loss or retention of heterozygosity and mutation screening.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156344"], "description"=>"<p>C-TL (<i>n</i> = 93) and G-TL (<i>n</i> = 16) were classified according to the LOH results at D12Mit132 (Proximal to <i>Bcl11b</i>) and D12nds2 (Distal to <i>Bcl11b</i>) on chromosome 12 combined with DNA copy number results from array CGH and/or DNA copy number RQ-PCRs at D12Mit132, D12nds2 and within <i>Bcl11b</i> (the remaining 8 C-TL samples had insufficient DNA for copy number screening). The frequencies of Telomeric Deletion LOH (deletion at both sites), Telomeric Recombination LOH (recombination at both sites) and Paired Deletion & Recombination (both mechanisms in either order) were similar for both carbon and gamma groups, yet the overall distribution of the classes was significantly different between carbon and gamma groups (P<0.0001, Pearson’s Chi-Squared) since although 5/16 gamma tumours (31%) retained both alleles either side of <i>Bcl11b</i> (Retained Heterozygosity), 0/93 carbons tumours retained both alleles (<i>P</i> = 0.0001, Fisher’s Exact). In contrast, 32/93 carbon tumours (34%) lost one allele at D12Mit132 (upstream of <i>Bcl11b</i>) and yet retained both alleles towards the telomere at D12nds2 (Interstitial Deletion or Recombination LOH) while this was not observed (0/16) in gamma tumours (<i>P</i> = 0.003, Fisher’s Exact).</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468912, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.g004", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Classification_of_tumours_by_mechanism_of_retention_loss_of_heterozygosity_at_markers_proximal_and_distal_to_Bcl11b_on_chromosome_12_/1468912", "title"=>"Classification of tumours by mechanism of retention/loss of heterozygosity at markers proximal and distal to <i>Bcl11b</i> on chromosome 12.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156345"], "description"=>"<p>All 117 tumours are sorted by the presence (1) or absence (0) of specific aberrations in <i>Notch1</i>, <i>Ikzf1</i>, <i>Pten</i>, <i>Trp53</i> and <i>Bcl11b</i>, with (-) denoting an unclear result. Patterns of activation/inactivation are highlighted by letter codes as shown in the key, for <i>Notch1</i> (A-E), <i>Ikzf1</i> (F-H) and <i>Pten</i> (I-K). Almost complete LOH at the <i>Bcl11b</i> locus can be observed, along with high frequency of <i>Notch1</i> aberrations. <i>Pten</i> aberrations, and particularly homozygous <i>Pten</i> mutations, are more frequently associated with tumours not carrying the combined 5′ Deletion and PEST mutation in <i>Notch1</i>.</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468913, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.g005", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patterns_of_Oncogene_Activation_and_TSG_Inactivation_/1468913", "title"=>"Patterns of Oncogene Activation and TSG Inactivation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156346"], "description"=>"<p>Copy number variations associated with recombination at the TCRβ, TCRγ, TCRα/δ, Skint, IgH, IgLκ and IgLλ loci are omitted for clarity. Where a locus is listed, the feature was observed within this gene, or the feature included this gene, as noted. Where the feature covered multiple genes and was not clearly associated with any one locus, no locus is listed. Although multiple tumours may be listed for any one feature, the precise nature of each copy number change varied between tumours. Where there is more than one of the same type of feature listed for the same chromosome, each feature represents a distinct chromosomal location.</p><p>Summary of DNA copy number aberrations identified in twenty C-TL and twelve G-TL.</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468914, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.t001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_DNA_copy_number_aberrations_identified_in_twenty_C_TL_and_twelve_G_TL_/1468914", "title"=>"Summary of DNA copy number aberrations identified in twenty C-TL and twelve G-TL.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156347"], "description"=>"<p><i>P</i> values shown are from Fisher’s Exact Test, with differences significant at the 0.05 level marked (*)</p><p>Comparative Incidence for Genetic Features found in G-TL and C-TL.</p>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468915, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0130666.t002", "stats"=>{"downloads"=>7, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparative_Incidence_for_Genetic_Features_found_in_G_TL_and_C_TL_/1468915", "title"=>"Comparative Incidence for Genetic Features found in G-TL and C-TL.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-30 02:53:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/2156348", "https://ndownloader.figshare.com/files/2156349", "https://ndownloader.figshare.com/files/2156350", "https://ndownloader.figshare.com/files/2156351", "https://ndownloader.figshare.com/files/2156352", "https://ndownloader.figshare.com/files/2156353", "https://ndownloader.figshare.com/files/2156354", "https://ndownloader.figshare.com/files/2156355", "https://ndownloader.figshare.com/files/2156356", "https://ndownloader.figshare.com/files/2156357", "https://ndownloader.figshare.com/files/2156358", "https://ndownloader.figshare.com/files/2156359", "https://ndownloader.figshare.com/files/2156360", "https://ndownloader.figshare.com/files/2156361", "https://ndownloader.figshare.com/files/2156362", "https://ndownloader.figshare.com/files/2156363", "https://ndownloader.figshare.com/files/2156364", "https://ndownloader.figshare.com/files/2156365", "https://ndownloader.figshare.com/files/2156366"], "description"=>"<div><p>Monitoring mice exposed to carbon ion radiotherapy provides an indirect method to evaluate the potential for second cancer induction in normal tissues outside the radiotherapy target volume, since such estimates are not yet possible from historical patient data. Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume (average linear energy transfer = 13 keV.μm<sup>-1</sup>) during patient radiotherapy protocols. The mice were monitored for the remainder of their lifespan, and a large number of T cell lymphomas that arose in these mice were analysed alongside those arising following an equivalent dose of <sup>137</sup>Cs gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of <i>Notch1</i>, <i>Ikzf1</i>, <i>Pten</i>, <i>Trp53</i> and <i>Bcl11b</i> genes, we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably <i>Pten</i> mutation frequency and loss of heterozygosity flanking <i>Bcl11b</i>, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. If such large interstitial chromosomal deletions are a characteristic lesion of carbon ion irradiation, even when using the low linear energy transfer radiation to which normal tissues are exposed in radiotherapy patients, understanding the dose-response and tissue specificity of such DNA damage could prove key to assessing second cancer risk in carbon ion radiotherapy patients.</p></div>", "links"=>[], "tags"=>["monoenergetic carbon ion radiotherapy beam", "tumours", "Bcl 11b", "radiotherapy patients", "patient data", "carbon ion radiotherapy patients", "DNA damage", "carbon ion radiotherapy", "Bcl 11b genes", "radiation quality", "Genetic analysis", "T cell lymphomas", "radiation groups", "13 keV .μm", "B 6C mice", "cancer induction", "radiotherapy target volume", "Carbon Ion Radiotherapy Monitoring mice", "patient radiotherapy protocols", "gamma", "genomic loci", "tumour volume", "Frequent Interstitial Chromosome Deletions", "Pten mutation frequency", "equivalent dose", "cancer risk", "radiation types", "Heavy Ion Medical Accelerator", "Energy transfer", "Trp 53", "carbon ion irradiation", "chromosomal deletions", "carbon ion", "Second Cancer Induction", "energy transfer radiation", "Normal Tissues", "tissue specificity"], "article_id"=>1468916, "categories"=>["Uncategorised"], "users"=>["Benjamin J. Blyth", "Shizuko Kakinuma", "Masaaki Sunaoshi", "Yoshiko Amasaki", "Shinobu Hirano-Sakairi", "Kanae Ogawa", "Ayana Shirakami", "Yi Shang", "Chizuru Tsuruoka", "Mayumi Nishimura", "Yoshiya Shimada"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0130666.s001", "https://dx.doi.org/10.1371/journal.pone.0130666.s002", "https://dx.doi.org/10.1371/journal.pone.0130666.s003", "https://dx.doi.org/10.1371/journal.pone.0130666.s004", "https://dx.doi.org/10.1371/journal.pone.0130666.s005", "https://dx.doi.org/10.1371/journal.pone.0130666.s006", "https://dx.doi.org/10.1371/journal.pone.0130666.s007", "https://dx.doi.org/10.1371/journal.pone.0130666.s008", "https://dx.doi.org/10.1371/journal.pone.0130666.s009", "https://dx.doi.org/10.1371/journal.pone.0130666.s010", "https://dx.doi.org/10.1371/journal.pone.0130666.s011", "https://dx.doi.org/10.1371/journal.pone.0130666.s012", "https://dx.doi.org/10.1371/journal.pone.0130666.s013", "https://dx.doi.org/10.1371/journal.pone.0130666.s014", "https://dx.doi.org/10.1371/journal.pone.0130666.s015", "https://dx.doi.org/10.1371/journal.pone.0130666.s016", "https://dx.doi.org/10.1371/journal.pone.0130666.s017", "https://dx.doi.org/10.1371/journal.pone.0130666.s018", "https://dx.doi.org/10.1371/journal.pone.0130666.s019"], "stats"=>{"downloads"=>57, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_Analysis_of_T_Cell_Lymphomas_in_Carbon_Ion_Irradiated_Mice_Reveals_Frequent_Interstitial_Chromosome_Deletions_Implications_for_Second_Cancer_Induction_in_Normal_Tissues_during_Carbon_Ion_Radiotherapy_/1468916", "title"=>"Genetic Analysis of T Cell Lymphomas in Carbon Ion-Irradiated Mice Reveals Frequent Interstitial Chromosome Deletions: Implications for Second Cancer Induction in Normal Tissues during Carbon Ion Radiotherapy", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-30 02:53:21"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"19", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"11", "cited-by"=>"1", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"8", "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"=>"12"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"7", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"13", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"18", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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