bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 3 from Phosphatase and Tensin Homologue Deleted on Chromosome 10 Deficiency Accelerates Tumor Induction in a Mouse Model of ErbB-2 Mammary Tumorigenesis
Authors: Dourdin Nathalie , Schade Babette , Lesurf Robert , Hallett Michael , Munn Robert J. , Cardiff Robert D. , Muller William J.
Published: March 2023

Supplementary Figure 3 from Phosphatase and Tensin Homologue Deleted on Chromosome 10 Deficiency Accelerates Tumor Induction in a Mouse Model of ErbB-2 Mammary Tumorigenesis
Supplementary Figure 2 from Concordant Epigenetic Silencing of Transforming Growth Factor-β Signaling Pathway Genes Occurs Early in Breast Carcinogenesis
Authors: Hinshelwood Rebecca A. , Huschtscha Lily I. , Melki John , Stirzaker Clare , Abdipranoto Andrea , Vissel Bryce , Ravasi Timothy , Wells Christine A. , Hume David A. , Reddel Roger R. , Clark Susan J.
Published: March 2023

Supplementary Figure 2 from Concordant Epigenetic Silencing of Transforming Growth Factor-β Signaling Pathway Genes Occurs Early in Breast Carcinogenesis
Supplementary Figure Legends 1-7 from Proteasome Inhibition Up-regulates p53 and Apoptosis-Inducing Factor in Chondrocytes Causing Severe Growth Retardation in Mice
Authors: Zaman Farasat , Menendez-Benito Victoria , Eriksson Emma , Chagin Andrei S. , Takigawa Masaharu , Fadeel Bengt , Dantuma Nico P. , Chrysis Dionisios , Sävendahl Lars
Published: March 2023

Supplementary Figure Legends 1-7 from Proteasome Inhibition Up-regulates p53 and Apoptosis-Inducing Factor in Chondrocytes Causing Severe Growth Retardation in Mice
Supplementary Array Data from Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays
Authors: Stark Mitchell , Hayward Nicholas
Published: March 2023

Supplementary Array Data from Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays
Supplementary Table 4 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers
Authors: Yamashita Satoshi , Takahashi Satoru , McDonell Nathalie , Watanabe Naoko , Niwa Tohru , Hosoya Kosuke , Tsujino Yoshimi , Shirai Tomoyuki , Ushijima Toshikazu
Published: March 2023

Supplementary Table 4 from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers
Supplementary Materials and Methods from Inhibition of RAS-Mediated Transformation and Tumorigenesis by Targeting the Downstream E3 Ubiquitin Ligase Seven in Absentia Homologue
Authors: Schmidt Rebecca L. , Park Cheol Hong , Ahmed Atique U. , Gundelach Justin H. , Reed Nanette R. , Cheng Shen , Knudsen Bruce E. , Tang Amy H.
Published: March 2023

Supplementary Materials and Methods from Inhibition of RAS-Mediated Transformation and Tumorigenesis by Targeting the Downstream E3 Ubiquitin Ligase Seven in Absentia Homologue
Supplementary Figure Legends 1-3 from Pyrimethamine Induces Apoptosis of Melanoma Cells via a Caspase and Cathepsin Double-Edged Mechanism
Authors: Giammarioli Anna Maria , Maselli Angela , Casagrande Andrea , Gambardella Lucrezia , Gallina Angelo , Spada Massimo , Giovannetti Antonello , Proietti Enrico , Malorni Walter , Pierdominici Marina
Published: March 2023

Supplementary Figure Legends 1-3 from Pyrimethamine Induces Apoptosis of Melanoma Cells via a Caspase and Cathepsin Double-Edged Mechanism
Supplementary Figure 3 from Pyrimethamine Induces Apoptosis of Melanoma Cells via a Caspase and Cathepsin Double-Edged Mechanism
Authors: Giammarioli Anna Maria , Maselli Angela , Casagrande Andrea , Gambardella Lucrezia , Gallina Angelo , Spada Massimo , Giovannetti Antonello , Proietti Enrico , Malorni Walter , Pierdominici Marina
Published: March 2023

Supplementary Figure 3 from Pyrimethamine Induces Apoptosis of Melanoma Cells via a Caspase and Cathepsin Double-Edged Mechanism
Supplementary Table 4 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer
Authors: Schmidt Marcus , Böhm Daniel , von Törne Christian , Steiner Eric , Puhl Alexander , Pilch Henryk , Lehr Hans-Anton , Hengstler Jan G. , Kölbl Heinz , Gehrmann Mathias
Published: March 2023

Supplementary Table 4 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer
Supplementary Table 2 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer
Authors: Schmidt Marcus , Böhm Daniel , von Törne Christian , Steiner Eric , Puhl Alexander , Pilch Henryk , Lehr Hans-Anton , Hengstler Jan G. , Kölbl Heinz , Gehrmann Mathias
Published: March 2023

Supplementary Table 2 from The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer
Supplementary Figures 1-3 from Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects
Authors: Banihashemi Behzad , Vlad Roxana , Debeljevic Branislav , Giles Anoja , Kolios Michael C. , Czarnota Gregory J.
Published: March 2023

Supplementary Figures 1-3 from Ultrasound Imaging of Apoptosis in Tumor Response: Novel Preclinical Monitoring of Photodynamic Therapy Effects
Supplementary Tables 1-8 from Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Authors: Izadpanah Reza , Kaushal Deepak , Kriedt Christopher , Tsien Fern , Patel Bindiya , Dufour Jason , Bunnell Bruce A.
Published: March 2023

Supplementary Tables 1-8 from Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Supplementary Table 2 from NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas
Authors: Shin Dong-Mi , Shaffer Daniel J. , Wang Hongsheng , Roopenian Derry C. , Morse Herbert C.
Published: March 2023

Supplementary Table 2 from NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas
Supplementary Figure 1 from Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Authors: Izadpanah Reza , Kaushal Deepak , Kriedt Christopher , Tsien Fern , Patel Bindiya , Dufour Jason , Bunnell Bruce A.
Published: March 2023

Supplementary Figure 1 from Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Supplementary Figure 1 Legend from Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Authors: Izadpanah Reza , Kaushal Deepak , Kriedt Christopher , Tsien Fern , Patel Bindiya , Dufour Jason , Bunnell Bruce A.
Published: March 2023

Supplementary Figure 1 Legend from Long-term In vitro Expansion Alters the Biology of Adult Mesenchymal Stem Cells
Supplementary Methods, Legends for Figures 1-8 and Tables 1-3 from Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Authors: Shimamura Takeshi , Li Danan , Ji Hongbin , Haringsma Henry J. , Liniker Elizabeth , Borgman Christa L. , Lowell April M. , Minami Yuko , McNamara Kate , Perera Samanthi A. , Zaghlul Sara , Thomas Roman K. , Greulich Heidi , Kobayashi Susumu , Chirieac Lucian R. , Padera Robert F. , Kubo Shigeto , Takahashi Masaya , Tenen Daniel G. , Meyerson Matthew , Wong Kwok-Kin , Shapiro Geoffrey I.
Published: March 2023

Supplementary Methods, Legends for Figures 1-8 and Tables 1-3 from Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Supplementary Table 3 from Pten Inactivation Accelerates Oncogenic K-ras–Initiated Tumorigenesis in a Mouse Model of Lung Cancer
Authors: Iwanaga Kentaro , Yang Yanan , Raso Maria Gabriela , Ma Lijiang , Hanna Amy E. , Thilaganathan Nishan , Moghaddam Seyed , Evans Christopher M. , Li Huaiguang , Cai Wei-Wen , Sato Mitsuo , Minna John D. , Wu Hong , Creighton Chad J. , Demayo Francesco J. , Wistuba Ignacio I. , Kurie Jonathan M.
Published: March 2023

Supplementary Table 3 from Pten Inactivation Accelerates Oncogenic K-ras–Initiated Tumorigenesis in a Mouse Model of Lung Cancer
Supplementary Figure 6 from Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Authors: Shimamura Takeshi , Li Danan , Ji Hongbin , Haringsma Henry J. , Liniker Elizabeth , Borgman Christa L. , Lowell April M. , Minami Yuko , McNamara Kate , Perera Samanthi A. , Zaghlul Sara , Thomas Roman K. , Greulich Heidi , Kobayashi Susumu , Chirieac Lucian R. , Padera Robert F. , Kubo Shigeto , Takahashi Masaya , Tenen Daniel G. , Meyerson Matthew , Wong Kwok-Kin , Shapiro Geoffrey I.
Published: March 2023

Supplementary Figure 6 from Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Supplementary Figures 1-3 from Distinct RAD51 Associations with RAD52 and BCCIP in Response to DNA Damage and Replication Stress
Authors: Wray Justin , Liu Jingmei , Nickoloff Jac A. , Shen Zhiyuan
Published: March 2023

Supplementary Figures 1-3 from Distinct RAD51 Associations with RAD52 and BCCIP in Response to DNA Damage and Replication Stress
Supplementary Figure 1 from Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Authors: Shimamura Takeshi , Li Danan , Ji Hongbin , Haringsma Henry J. , Liniker Elizabeth , Borgman Christa L. , Lowell April M. , Minami Yuko , McNamara Kate , Perera Samanthi A. , Zaghlul Sara , Thomas Roman K. , Greulich Heidi , Kobayashi Susumu , Chirieac Lucian R. , Padera Robert F. , Kubo Shigeto , Takahashi Masaya , Tenen Daniel G. , Meyerson Matthew , Wong Kwok-Kin , Shapiro Geoffrey I.
Published: March 2023

Supplementary Figure 1 from Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Supplementary Figure 2 from Multiple Alternative Splicing Markers for Ovarian Cancer
Authors: Klinck Roscoe , Bramard Anne , Inkel Lyna , Dufresne-Martin Geneviève , Gervais-Bird Julien , Madden Richard , Paquet Éric R. , Koh ChuShin , Venables Julian P. , Prinos Panagiotis , Jilaveanu-Pelmus Manuela , Wellinger Raymund , Rancourt Claudine , Chabot Benoit , Abou Elela Sherif
Published: March 2023

Supplementary Figure 2 from Multiple Alternative Splicing Markers for Ovarian Cancer
Legends to Supplementary Tables and Figures from Multiple Alternative Splicing Markers for Ovarian Cancer
Authors: Klinck Roscoe , Bramard Anne , Inkel Lyna , Dufresne-Martin Geneviève , Gervais-Bird Julien , Madden Richard , Paquet Éric R. , Koh ChuShin , Venables Julian P. , Prinos Panagiotis , Jilaveanu-Pelmus Manuela , Wellinger Raymund , Rancourt Claudine , Chabot Benoit , Abou Elela Sherif
Published: March 2023

Legends to Supplementary Tables and Figures from Multiple Alternative Splicing Markers for Ovarian Cancer
Supplementary Figure 2 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence
Authors: Kumamoto Kensuke , Spillare Elisa A. , Fujita Kaori , Horikawa Izumi , Yamashita Taro , Appella Ettore , Nagashima Makoto , Takenoshita Seiichi , Yokota Jun , Harris Curtis C.
Published: March 2023

Supplementary Figure 2 from Nutlin-3a Activates p53 to Both Down-regulate Inhibitor of Growth 2 and Up-regulate mir-34a, mir-34b, and mir-34c Expression, and Induce Senescence
Supplementary Figure 2 from Imaging Pharmacodynamics of the α-Folate Receptor–Targeted Thymidylate Synthase Inhibitor BGC 945
Authors: Pillai Radhakrishna G. , Forster Martin , Perumal Meg , Mitchell Fraser , Leyton Julius , Aibgirhio Franklin I. , Golovko Oksana , Jackman Ann L. , Aboagye Eric O.
Published: March 2023

Supplementary Figure 2 from Imaging Pharmacodynamics of the α-Folate Receptor–Targeted Thymidylate Synthase Inhibitor BGC 945
Supplementary Table 1 from Effect of Ablation or Inhibition of Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent on Genetic Background
Authors: Martin Michelle D. , Carter Kathy J. , Jean-Philippe Sharon R. , Chang Mayland , Mobashery Shahriar , Thiolloy Sophie , Lynch Conor C. , Matrisian Lynn M. , Fingleton Barbara
Published: March 2023

Supplementary Table 1 from Effect of Ablation or Inhibition of Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent on Genetic Background
Supplementary Figure 4 from Complement-Dependent Tumor Cell Lysis Triggered by Combinations of Epidermal Growth Factor Receptor Antibodies
Authors: Dechant Michael , Weisner Wencke , Berger Sven , Peipp Matthias , Beyer Thomas , Schneider-Merck Tanja , Lammerts van Bueren Jeroen J. , Bleeker Wim K. , Parren Paul W.H.I. , van de Winkel Jan G.J. , Valerius Thomas
Published: March 2023

Supplementary Figure 4 from Complement-Dependent Tumor Cell Lysis Triggered by Combinations of Epidermal Growth Factor Receptor Antibodies
Supplementary Figure 1 from Bortezomib (Velcade) Induces p27Kip1 Expression through S-Phase Kinase Protein 2 Degradation in Colorectal Cancer
Authors: Uddin Shahab , Ahmed Maqbool , Bavi Prashant , El-Sayed Raafat , Al-Sanea Nasser , AbdulJabbar Alaa , Ashari Luai H. , Alhomoud Samar , Al-Dayel Fouad , Hussain Azhar R. , Al-Kuraya Khawla S.
Published: March 2023

Supplementary Figure 1 from Bortezomib (Velcade) Induces p27Kip1 Expression through S-Phase Kinase Protein 2 Degradation in Colorectal Cancer
Supplementary Table 1 from Lack of Hypoxic Response in Uterine Leiomyomas despite Severe Tissue Hypoxia
Authors: Mayer Arnulf , Höckel Michael , Wree Alexander , Leo Cornelia , Horn Lars-Christian , Vaupel Peter
Published: March 2023

Supplementary Table 1 from Lack of Hypoxic Response in Uterine Leiomyomas despite Severe Tissue Hypoxia
Supplementary Table 1 from Transforming Growth Factor-β Suppresses the Ability of Ski to Inhibit Tumor Metastasis by Inducing Its Degradation
Authors: Le Scolan Erwan , Zhu Qingwei , Wang Long , Bandyopadhyay Abhik , Javelaud Delphine , Mauviel Alain , Sun LuZhe , Luo Kunxin
Published: March 2023

Supplementary Table 1 from Transforming Growth Factor-β Suppresses the Ability of Ski to Inhibit Tumor Metastasis by Inducing Its Degradation
Supplementary Table 2 from A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
Authors: Bonome Tomas , Levine Douglas A. , Shih Joanna , Randonovich Mike , Pise-Masison Cindy A. , Bogomolniy Faina , Ozbun Laurent , Brady John , Barrett J. Carl , Boyd Jeff , Birrer Michael J.
Published: March 2023

Supplementary Table 2 from A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
Supplementary Figure 3a from Aplidin, a Marine Organism–Derived Compound with Potent Antimyeloma Activity In vitro and In vivo
Authors: Mitsiades Constantine S. , Ocio Enrique M. , Pandiella Atanasio , Maiso Patricia , Gajate Consuelo , Garayoa Mercedes , Vilanova David , Montero Juan Carlos , Mitsiades Nicholas , McMullan Ciaran J. , Munshi Nikhil C. , Hideshima Teru , Chauhan Dharminder , Aviles Pablo , Otero Gabriel , Faircloth Glynn , Mateos M. Victoria , Richardson Paul G. , Mollinedo Faustino , San-Miguel Jesus F. , Anderson Kenneth C.
Published: March 2023

Supplementary Figure 3a from Aplidin, a Marine Organism–Derived Compound with Potent Antimyeloma Activity In vitro and In vivo
Supplementary Figure 2 from A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
Authors: Bonome Tomas , Levine Douglas A. , Shih Joanna , Randonovich Mike , Pise-Masison Cindy A. , Bogomolniy Faina , Ozbun Laurent , Brady John , Barrett J. Carl , Boyd Jeff , Birrer Michael J.
Published: March 2023

Supplementary Figure 2 from A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
Supplementary Tables 1-2, Figures 1-15 from Vascular Endothelial Cadherin Promotes Breast Cancer Progression via Transforming Growth Factor β Signaling
Authors: Labelle Myriam , Schnittler Hans J. , Aust Daniela E. , Friedrich Katrin , Baretton Gustavo , Vestweber Dietmar , Breier Georg
Published: March 2023

Supplementary Tables 1-2, Figures 1-15 from Vascular Endothelial Cadherin Promotes Breast Cancer Progression via Transforming Growth Factor β Signaling
Supplementary Table 3 from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Authors: Coates Philip J. , Rundle Jana K. , Lorimore Sally A. , Wright Eric G.
Published: March 2023

Supplementary Table 3 from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Supplementary Table 2 from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Authors: Coates Philip J. , Rundle Jana K. , Lorimore Sally A. , Wright Eric G.
Published: March 2023

Supplementary Table 2 from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Supplementary Table 1 from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Authors: Coates Philip J. , Rundle Jana K. , Lorimore Sally A. , Wright Eric G.
Published: March 2023

Supplementary Table 1 from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Supplementary Figure 4 from Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells
Authors: Darido Charbel , Buchert Michael , Pannequin Julie , Bastide Pauline , Zalzali Hassan , Mantamadiotis Theo , Bourgaux Jean-François , Garambois Véronique , Jay Philippe , Blache Philippe , Joubert Dominique , Hollande Frédéric
Published: March 2023

Supplementary Figure 4 from Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells
Supplementary Figure 1 from Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells
Authors: Darido Charbel , Buchert Michael , Pannequin Julie , Bastide Pauline , Zalzali Hassan , Mantamadiotis Theo , Bourgaux Jean-François , Garambois Véronique , Jay Philippe , Blache Philippe , Joubert Dominique , Hollande Frédéric
Published: March 2023

Supplementary Figure 1 from Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells
Supplementary Figure 2 from Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays
Authors: Nancarrow Derek J. , Handoko Herlina Y. , Smithers B. Mark , Gotley David C. , Drew Paul A. , Watson David I. , Clouston Andrew D. , Hayward Nicholas K. , Whiteman David C.
Published: March 2023

Supplementary Figure 2 from Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays
Supplementary Methods and Figures 1-2 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Authors: Osada Hirotaka , Tomida Shuta , Yatabe Yasushi , Tatematsu Yoshio , Takeuchi Toshiyuki , Murakami Hideki , Kondo Yutaka , Sekido Yoshitaka , Takahashi Takashi
Published: March 2023

Supplementary Methods and Figures 1-2 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Supplementary Figure 2 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Authors: Osada Hirotaka , Tomida Shuta , Yatabe Yasushi , Tatematsu Yoshio , Takeuchi Toshiyuki , Murakami Hideki , Kondo Yutaka , Sekido Yoshitaka , Takahashi Takashi
Published: March 2023

Supplementary Figure 2 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Supplementary Figure 1 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Authors: Osada Hirotaka , Tomida Shuta , Yatabe Yasushi , Tatematsu Yoshio , Takeuchi Toshiyuki , Murakami Hideki , Kondo Yutaka , Sekido Yoshitaka , Takahashi Takashi
Published: March 2023

Supplementary Figure 1 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Supplementary Tables 1-4 from Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer
Authors: Schepeler Troels , Reinert Jørgen T. , Ostenfeld Marie S. , Christensen Lise L. , Silahtaroglu Asli N. , Dyrskjøt Lars , Wiuf Carsten , Sørensen Frank J. , Kruhøffer Mogens , Laurberg Søren , Kauppinen Sakari , Ørntoft Torben F. , Andersen Claus L.
Published: March 2023

Supplementary Tables 1-4 from Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer
Supplementary Table 4 from Frequent Inactivation of a Putative Tumor Suppressor, Angiopoietin-Like Protein 2, in Ovarian Cancer
Authors: Kikuchi Ryoko , Tsuda Hitoshi , Kozaki Ken-ichi , Kanai Yae , Kasamatsu Takahiro , Sengoku Kazuo , Hirohashi Setsuo , Inazawa Johji , Imoto Issei
Published: March 2023

Supplementary Table 4 from Frequent Inactivation of a Putative Tumor Suppressor, Angiopoietin-Like Protein 2, in Ovarian Cancer
Supplementary Table 2 from Frequent Inactivation of a Putative Tumor Suppressor, Angiopoietin-Like Protein 2, in Ovarian Cancer
Authors: Kikuchi Ryoko , Tsuda Hitoshi , Kozaki Ken-ichi , Kanai Yae , Kasamatsu Takahiro , Sengoku Kazuo , Hirohashi Setsuo , Inazawa Johji , Imoto Issei
Published: March 2023

Supplementary Table 2 from Frequent Inactivation of a Putative Tumor Suppressor, Angiopoietin-Like Protein 2, in Ovarian Cancer
Supplementary Text 3 from Cell Lineage Analysis of a Mouse Tumor
Authors: Frumkin Dan , Wasserstrom Adam , Itzkovitz Shalev , Stern Tomer , Harmelin Alon , Eilam Raya , Rechavi Gideon , Shapiro Ehud
Published: March 2023

Supplementary Text 3 from Cell Lineage Analysis of a Mouse Tumor
Supplementary Text 2 from Cell Lineage Analysis of a Mouse Tumor
Authors: Frumkin Dan , Wasserstrom Adam , Itzkovitz Shalev , Stern Tomer , Harmelin Alon , Eilam Raya , Rechavi Gideon , Shapiro Ehud
Published: March 2023

Supplementary Text 2 from Cell Lineage Analysis of a Mouse Tumor
Supplementary Figure 3 from Subtypes of Breast Cancer Show Preferential Site of Relapse
Authors: Smid Marcel , Wang Yixin , Zhang Yi , Sieuwerts Anieta M. , Yu Jack , Klijn Jan G.M. , Foekens John A. , Martens John W.M.
Published: March 2023

Supplementary Figure 3 from Subtypes of Breast Cancer Show Preferential Site of Relapse
Supplementary Figure Legends 1-2 from Skewing the T-Cell Repertoire by Combined DNA Vaccination, Host Conditioning, and Adoptive Transfer
Authors: Jorritsma Annelies , Bins Adriaan D. , Schumacher Ton N.M. , Haanen John B.A.G.
Published: March 2023

Supplementary Figure Legends 1-2 from Skewing the T-Cell Repertoire by Combined DNA Vaccination, Host Conditioning, and Adoptive Transfer
Supplementary Figure 1 from Skewing the T-Cell Repertoire by Combined DNA Vaccination, Host Conditioning, and Adoptive Transfer
Authors: Jorritsma Annelies , Bins Adriaan D. , Schumacher Ton N.M. , Haanen John B.A.G.
Published: March 2023

Supplementary Figure 1 from Skewing the T-Cell Repertoire by Combined DNA Vaccination, Host Conditioning, and Adoptive Transfer
Supplementary Figure 1 from Curcumin Blocks RON Tyrosine Kinase–Mediated Invasion of Breast Carcinoma Cells
Authors: Narasimhan Madhusudhanan , Ammanamanchi Sudhakar
Published: March 2023

Supplementary Figure 1 from Curcumin Blocks RON Tyrosine Kinase–Mediated Invasion of Breast Carcinoma Cells
Supplementary Figures 1A and 1B from A Retroinhibition Approach Reveals a Tumor Cell–Autonomous Response to Rapamycin in Head and Neck Cancer
Authors: Amornphimoltham Panomwat , Patel Vyomesh , Leelahavanichkul Kantima , Abraham Robert T. , Gutkind J. Silvio
Published: March 2023

Supplementary Figures 1A and 1B from A Retroinhibition Approach Reveals a Tumor Cell–Autonomous Response to Rapamycin in Head and Neck Cancer
Supplementary Figure 1 from RAP80 Responds to DNA Damage Induced by Both Ionizing Radiation and UV Irradiation and Is Phosphorylated at Ser205
Authors: Yan Jun , Yang Xiao-Ping , Kim Yong-Sik , Jetten Anton M.
Published: March 2023

Supplementary Figure 1 from RAP80 Responds to DNA Damage Induced by Both Ionizing Radiation and UV Irradiation and Is Phosphorylated at Ser205
Supplementary Figure 1 from Microphthalmia-Associated Transcription Factor Is a Critical Transcriptional Regulator of Melanoma Inhibitor of Apoptosis in Melanomas
Authors: Dynek Jasmin N. , Chan Sara M. , Liu Jinfeng , Zha Jiping , Fairbrother Wayne J. , Vucic Domagoj
Published: March 2023

Supplementary Figure 1 from Microphthalmia-Associated Transcription Factor Is a Critical Transcriptional Regulator of Melanoma Inhibitor of Apoptosis in Melanomas
Supplementary Figure 2 from Peroxisome Proliferator-Activated Receptor-δ Induces Cell Proliferation by a Cyclin E1–Dependent Mechanism and Is Up-regulated in Thyroid Tumors
Authors: Zeng Lingchun , Geng Yan , Tretiakova Maria , Yu Xuemei , Sicinski Peter , Kroll Todd G.
Published: March 2023

Supplementary Figure 2 from Peroxisome Proliferator-Activated Receptor-δ Induces Cell Proliferation by a Cyclin E1–Dependent Mechanism and Is Up-regulated in Thyroid Tumors
Data from Genetic Determinants of Somatic Selection of Mutational Processes in 3,566 Human Cancers
Authors: Guo Jintao , Zhou Ying , Xu Chaoqun , Chen Qinwei , Sztupinszki Zsófia , Börcsök Judit , Xu Canqiang , Ye Feng , Tang Weiwei , Kang Jiapeng , Yang Lu , Zhong Jiaxin , Zhong Taoling , Hu Tianhui , Yu Rongshan , Szallasi Zoltan , Deng Xianming , Li Qiyuan
Published: March 2023

Abstract
The somatic landscape of the cancer genome results from different mutational processes represented by distinct “mutational signatures.” Although several mutagenic mechanisms are known to cause specific mutational signatures in cell lines, the variation of somatic mutational activities in patients, which is mostly attributed to somatic selection, is still poorly explained. Here, we introduce a quantitative trait, mutational propensity (MP), and describe an integrated method to infer genetic determinants of variations in the mutational processes in 3,566 cancers with specific underlying mechanisms. As a result, we report 2,314 candidate determinants with both significant germline and somatic effects on somatic selection of mutational processes, of which, 485 act via cancer gene expression and 1,427 act through the tumor–immune microenvironment. These data demonstrate that the genetic determinants of MPs provide complementary information to known cancer driver genes, clonal evolution, and clinical biomarkers.
Significance:
The genetic determinants of the somatic mutational processes in cancer elucidate the biology underlying somatic selection and evolution of cancers and demonstrate complementary predictive power across cancer types.
Data from A Systematic Review and Multilevel Regression Analysis Reveals the Comorbidity Prevalence in Cancer
Authors: Vrinzen Cilla E.J. , Delfgou Linn , Stadhouders Niek , Hermens Rosella P.M.G. , Merkx Matthias A.W. , Bloemendal Haiko J. , Jeurissen Patrick P.T.
Published: March 2023

Abstract
Comorbidities can have major implications for cancer care, as they might impact the timing of cancer diagnosis, compromise optimal care, affect treatment outcomes, and increase healthcare costs. Thus, it is important to comprehensively evaluate cancer comorbidities and examine trends over time. Here, we performed a systematic literature review on the prevalence and types of comorbidities for the five most common forms of cancer. Observational studies from Organisation for Economic Co-operation and Development countries published between 1990 and 2020 in English or Dutch that used routinely collected data from a representative population were included. The search yielded 3,070 articles, of which, 161 were eligible for data analyses. Multilevel analyses were performed to evaluate determinants of variation in comorbidity prevalence and trends over time. The weighted average comorbidity prevalence was 33.4%, and comorbidities were the most common in lung cancer (46.7%) and colorectal cancer (40.0%), followed by prostate cancer (28.5%), melanoma cancer (28.3%), and breast cancer (22.4%). The most common types of comorbidities were hypertension (29.7%), pulmonary diseases (15.9%), and diabetes (13.5%). After adjusting for gender, type of comorbidity index, age, data source (patient records vs. claims), and country, a significant increase in comorbidities of 0.54% per year was observed. Overall, a large and increasing proportion of the oncologic population is dealing with comorbidities, which could be used to inform and adapt treatment options to improve health outcomes and reduce healthcare costs.
Significance:
Comorbidities are frequent and increasing in patients with cancer, emphasizing the importance of exploring optimal ways for uniform comorbidity registration and incorporating comorbidity management into cancer care.
Data from WNT5a Signaling through ROR2 Activates the Hippo Pathway to Suppress YAP1 Activity and Tumor Growth
Authors: Wang Keshan , Ma Fen , Arai Seiji , Wang Yun , Varkaris Andreas , Poluben Larysa , Voznesensky Olga , Xie Fang , Zhang Xiaoping , Yuan Xin , Balk Steven P.
Published: March 2023

Abstract
Noncanonical Wnt signaling by WNT5a has oncogenic and tumor suppressive activities, but downstream pathways mediating these specific effects remain to be fully established. In a subset of prostate cancer organoid culture and xenograft models, inhibition of Wnt synthesis stimulated growth, whereas WNT5a or a WNT5a mimetic peptide (Foxy5) markedly suppressed tumor growth. WNT5a caused a ROR2-dependent decrease in YAP1 activity, which was associated with increased phosphorylation of MST1/2, LATS1, MOB1, and YAP1, indicating Hippo pathway activation. Deletion of MST1/2 abrogated the WNT5a response. WNT5a similarly activated Hippo in ROR2-expressing melanoma cells, whereas WNT5a in ROR2-negative cells suppressed Hippo. This suppression was associated with increased inhibitory phosphorylation of NF2/Merlin that was not observed in ROR2-expressing cells. WNT5a also increased mRNA encoding Hippo pathway components including MST1 and MST2 and was positively correlated with these components in prostate cancer clinical datasets. Conversely, ROR2 and WNT5a expression was stimulated by YAP1, and correlated with increased YAP1 activity in clinical datasets, revealing a WNT5a/ROR2 negative feedback loop to modulate YAP1 activity. Together these findings identify Hippo pathway activation as a mechanism that mediates the tumor suppressive effects of WNT5a and indicate that expression of ROR2 may be a predictive biomarker for responsiveness to WNT5a-mimetic drugs.
Significance:
WNT5a signaling through ROR2 activates the Hippo pathway to downregulate YAP1/TAZ activity and suppress tumor growth, identifying ROR2 as a potential biomarker to identify patients that could benefit from WNT5a-related agents.
Data from Mutations in Apc and p53 Synergize to Promote Mammary Neoplasia
Authors: Méniel Valérie , Hay Trevor , Douglas-Jones Anthony , Sansom Owen J. , Clarke Alan R.
Published: March 2023

Abstract
Mutations of Apc and p53 have both been implicated in human and murine mammary neoplasia. To investigate potential interactions between Apc and p53, we conditionally inactivated Apc in both the presence and the absence of functional p53. Apc deficiency on its own leads to the development of metaplasia but not neoplasia. We show here that these areas of metaplasia are characterized by elevated levels of both p53 and p21. In the additional absence of p53,there is rapid progression to neoplasia, with 44.4% of lymphoma-free mice developing a mammary tumor with earliest observed onset at pregnancy. To investigate the mechanism by which p53 deficiency accelerates neoplasia, we used the Rosa26R reporter strain as a marker of Cre-mediated recombination and show a role for p53 in the loss of Apc-deficient cells. This role seems limited to pregnancy and subsequent time points. We therefore show clear synergy between these two mutations in mammary gland neoplasia and present data to suggest that at least one mechanism for this acceleration is the p53-dependent loss of Apc-deficient cells.
Data from Cellular Targets of Gefitinib
Authors: Brehmer Dirk , Greff Zoltán , Godl Klaus , Blencke Stephanie , Kurtenbach Alexander , Weber Martina , Müller Stefan , Klebl Bert , Cotten Matt , Kéri György , Wissing Josef , Daub Henrik
Published: March 2023

Abstract
Targeted inhibition of protein kinases with small molecule drugs has evolved into a viable approach for anticancer therapy. However, the true selectivity of these therapeutic agents has remained unclear. Here, we used a proteomic method to profile the cellular targets of the clinical epidermal growth factor receptor kinase inhibitor gefitinib. Our data suggest alternative cellular modes of action for gefitinib and provide rationales for the development of related drugs.
Data from Functional Evaluation and Cancer Risk Assessment of BRCA2 Unclassified Variants
Authors: Wu Kangjian , Hinson Shannon R. , Ohashi Akihiro , Farrugia Daniel , Wendt Patricia , Tavtigian Sean V. , Deffenbaugh Amie , Goldgar David , Couch Fergus J.
Published: March 2023

Abstract
The influence of germ line BRCA2 unclassified variants (UCV), including missense mutations and in-frame deletions and insertions on BRCA2 function and on cancer risk, has not been defined although these mutations account for 43% of all identified BRCA2 sequence alterations. To investigate the effects of UCVs on BRCA2 function, we compared mutant and wild-type forms of BRCA2 using assays of cellular survival and viability, homologous recombination repair, and genome instability. We confirm that the effects of known deleterious mutations can be distinguished from neutral polymorphisms and wild-type BRCA2 in these assays, and we characterize the influence of a series of UCVs on BRCA2 function. We also describe how the results from the assays can be combined with data from analysis of cosegregation of the UCVs with cancer, co-occurrence of the UCVs with other deleterious mutations, and interspecies sequence variation in a comprehensive framework in an effort to better distinguish between disease predisposing and neutral UCVs. This combined approach represents a useful means of addressing the functional significance and cancer relevance of UCVs in BRCA2.
Data from PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma
Authors: Saal Lao H. , Holm Karolina , Maurer Matthew , Memeo Lorenzo , Su Tao , Wang Xiaomei , Yu Jennifer S. , Malmström Per-Olof , Mansukhani Mahesh , Enoksson Jens , Hibshoosh Hanina , Borg Åke , Parsons Ramon
Published: March 2023

Abstract
Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit α of PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations in 26% of 342 human breast tumor samples and cell lines at about equal frequency in tumor stages I to IV. To investigate the relationship between PTEN and PIK3CA, we generated a cohort of tumors that had lost PTEN expression and compared it with a matched control set that had retained PTEN. A highly significant association between PIK3CA mutations and retention of PTEN protein expression was observed. In addition, PIK3CA mutations were associated with expression of estrogen and progesterone receptors (ER/PR), lymph node metastasis, and ERBB2 overexpression. The fact that PIK3CA mutations and PTEN loss are nearly mutually exclusive implies that deregulated phosphatidylinositol-3,4,5-triphosphate (PIP3) is critical for tumorigenesis in a significant fraction of breast cancers and that loss of PIP3 homeostasis by abrogation of either PIK3CA or PTEN relieves selective pressure for targeting of the other gene. The correlation of PIK3CA mutation to ER/PR-positive tumors and PTEN loss to ER/PR-negative tumors argues for disparate branches of tumor evolution. Furthermore, the association between ERBB2 overexpression and PIK3CA mutation implies that more than one input activating the PI3K/AKT pathway may be required to overcome intact PTEN. Thus, mutation of PIK3CA is frequent, occurs early in carcinoma development, and has prognostic and therapeutic implications.
Data from TGFβ Signaling Activated by Cancer-Associated Fibroblasts Determines the Histological Signature of Lung Adenocarcinoma
Authors: Sato Ryo , Imamura Kosuke , Semba Takashi , Tomita Yusuke , Saeki Sho , Ikeda Koei , Komohara Yoshihiro , Suzuki Makoto , Sakagami Takuro , Saya Hideyuki , Arima Yoshimi
Published: March 2023

Abstract
Invasive lung adenocarcinoma (LADC) can be classified histologically as lepidic, acinar, papillary, micropapillary, or solid. Most LADC tumors manifest several of these histological subtypes, with heterogeneity being related to therapeutic resistance. We report here that in immunodeficient mice, human LADC cells form tumors with distinct histological features, MUC5AC-expressing solid-type or cytokeratin 7 (CK7)-expressing acinar-type tumors, depending on the site of development, and that a solid-to-acinar transition (SAT) could be induced by the tumor microenvironment. The TGFβ-Smad signaling pathway was activated in both tumor and stromal cells of acinar-type tumors. Immortalized cancer-associated fibroblasts (CAF) derived from acinar-type tumors induced SAT in 3D cocultures with LADC cells. Exogenous TGFβ1 or overexpression of an active form of TGFβ1 increased CK7 expression and reduced MUC5AC expression in LADC cells, and knockdown of Tgfb1 mRNA in CAFs attenuated SAT induction. RNA-sequencing analysis suggested that angiogenesis and neutrophil recruitment are associated with SAT in vivo. Our data indicate that CAF-mediated paracrine TGFβ signaling induces remodeling of tumor tissue and determines the histological pattern of LADC, thereby contributing to tumor heterogeneity.
Significance:
CAFs secrete TGFβ to induce a solid-to-acinar transition in lung cancer cells, demonstrating how the tumor microenvironment influences histological patterns and tumor heterogeneity in lung adenocarcinoma.
Data from Lentiviral-Driven Discovery of Cancer Drug Resistance Mutations
Authors: Yenerall Paul , Kollipara Rahul K. , Avila Kimberley , Peyton Michael , Eide Christopher A. , Bottomly Daniel , McWeeney Shannon K. , Liu Yan , Westover Kenneth D. , Druker Brian J. , Minna John D. , Kittler Ralf
Published: March 2023

Abstract
Identifying resistance mutations in a drug target provides crucial information. Lentiviral transduction creates multiple types of mutations due to the error-prone nature of the HIV-1 reverse transcriptase (RT). Here we optimized and leveraged this property to identify drug resistance mutations, developing a technique we term LentiMutate. This technique was validated by identifying clinically relevant EGFR resistance mutations, then applied to two additional clinical anticancer drugs: imatinib, a BCR-ABL inhibitor, and AMG 510, a KRAS G12C inhibitor. Novel deletions in BCR-ABL1 conferred resistance to imatinib. In KRAS-G12C or wild-type KRAS, point mutations in the AMG 510 binding pocket or oncogenic non-G12C mutations conferred resistance to AMG 510. LentiMutate should prove highly valuable for clinical and preclinical cancer-drug development.
Significance:
LentiMutate can evaluate a drug's on-target activity and can nominate resistance mutations before they occur in patients, which could accelerate and refine drug development to increase the survival of patients with cancer.
Data from OLIG2 (BHLHB1), a bHLH Transcription Factor, Contributes to Leukemogenesis in Concert with LMO1
Authors: Lin Ying-Wei , Deveney Ramona , Barbara Mary , Iscove Norman N. , Nimer Stephen D. , Slape Christopher , Aplan Peter D.
Published: March 2023

Abstract
OLIG2 (originally designated BHLHB1) encodes a transcription factor that contains the basic helix-loop-helix motif. Although expression of OLIG2 is normally restricted to neural tissues, overexpression of OLIG2 has been shown in patients with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T LBL). In the current study, we found that overexpression of OLIG2 was not only found in oligodendroglioma samples and normal neural tissue but also in a wide spectrum of malignant cell lines including leukemia, non–small cell lung carcinoma, melanoma, and breast cancer cell lines. To investigate whether enforced expression of OLIG2 is oncogenic, we generated transgenic mice that overexpressed OLIG2 in the thymus. Ectopic OLIG2 expression in the thymus was only weakly oncogenic as only 2 of 85 mice developed pre-T LBL. However, almost 60% of transgenic mice that overexpressed both OLIG2 and LMO1 developed pre-T LBL with large thymic tumor masses. Gene expression profiling of thymic tumors that developed in OLIG2/LMO1 mice revealed up-regulation of Notch1 as well as Deltex1 (Dtx1) and pre T-cell antigen receptor α (Ptcra), two genes that are considered to be downstream of Notch1. Of note, we found mutations in the Notch1 heterodimerization or proline-, glutamic acid-, serine-, and threonine-rich domain in three of six primary thymic tumors. In addition, growth of leukemic cell lines established from OLIG2/LMO1 transgenic mice was suppressed by a γ-secretase inhibitor, suggesting that Notch1 up-regulation is important for the proliferation of OLIG2-LMO1 leukemic cells.
Data from From Mice to Humans
Authors: Hu Yuhui , Sun Hongxia , Drake Jeffrey , Kittrell Frances , Abba Martin C. , Deng Li , Gaddis Sally , Sahin Aysegul , Baggerly Keith , Medina Daniel , Aldaz C. Marcelo
Published: March 2023

Abstract
Genetically engineered mouse mammary cancer models have been used over the years as systems to study human breast cancer. However, much controversy exists on the utility of such models as valid equivalents to the human cancer condition. To perform an interspecies gene expression comparative study in breast cancer we used a mouse model that most closely resembles human breast carcinogenesis. This system relies on the transplant of p53 null mouse mammary epithelial cells into the cleared mammary fat pads of syngeneic hosts. Serial analysis of gene expression (SAGE) was used to obtain gene expression profiles of normal and tumor samples from this mouse mammary cancer model (>300,000 mouse mammary-specific tags). The resulting mouse data were compared with 25 of our human breast cancer SAGE libraries (>2.5 million human breast-specific tags). We observed significant similarities in the deregulation of specific genes and gene families when comparing mouse with human breast cancer SAGE data. A total of 72 transcripts were identified as commonly deregulated in both species. We observed a systematic and significant down-regulation in all of the tumors from both species of various cytokines, including CXCL1 (GRO1), LIF, interleukin 6, and CCL2. All of the mouse and most human mammary tumors also displayed decreased expression of genes known to inhibit cell proliferation, including NFKBIA (IKBα), GADD45B, and CDKN1A (p21); transcription-related genes such as CEBP, JUN, JUNB, and ELF1; and apoptosis-related transcripts such as IER3 and GADD34/PPP1R15A. Examples of overexpressed transcripts in tumors from both species include proliferation-related genes such as CCND1, CKS1B, and STMN1 (oncoprotein 18); and genes related to other functions such as SEPW1, SDFR1, DNCI2, and SP110. Importantly, abnormal expression of several of these genes has not been associated previously with breast cancer. The consistency of these observations was validated in independent mouse and human mammary cancer sets.

This is the first interspecies comparison of mammary cancer gene expression profiles. The comparative analysis of mouse and human SAGE mammary cancer data validates this p53 null mouse tumor model as a useful system closely resembling human breast cancer development and progression. More importantly, these studies are allowing us to identify relevant biomarkers of potential use in human studies while leading to a better understanding of specific mechanisms of human breast carcinogenesis.
Data from DNA Hypomethylation and Ovarian Cancer Biology
Authors: Widschwendter Martin , Jiang Guanchao , Woods Christian , Müller Hannes M. , Fiegl Heidi , Goebel Georg , Marth Christian , Müller-Holzner Elisabeth , Zeimet Alain G. , Laird Peter W. , Ehrlich Melanie
Published: March 2023

Abstract
Hypomethylation of some portions of the genome and hypermethylation of others are very frequent in human cancer. The hypomethylation often involves satellite 2 (Sat2) DNA in the juxtacentromeric (centromere-adjacent) region of chromosome 1. In this study, we analyzed methylation in centromeric and juxtacentromeric satellite DNA in 115 ovarian cancers, 26 non-neoplastic ovarian specimens, and various normal somatic tissue standards. We found that hypomethylation of both types of satellite DNA in ovarian samples increased significantly from non-neoplastic toward cancer tissue. Furthermore, strong hypomethylation was significantly more prevalent in tumors of advanced stage or high grade. Importantly, extensive hypomethylation of Sat2 DNA in chromosome 1 was a highly significant marker of poor prognosis (relative risk for relapse, 4.1, and death, 9.4) and more informative than tumor grade or stage. Also, comparing methylation of satellite DNA and 15 5′ gene regions, which are often hypermethylated in cancer or implicated in ovarian carcinogenesis, we generally found no positive or negative association between methylation changes in satellite DNA and in the gene regions. However, hypermethylation at two loci, CDH13 (at 16q24) and RNR1 (at 13p12), was correlated strongly with lower levels of Sat2 hypomethylation. The CDH13/Sat2 epigenetic correlation was seen also in breast cancers. We conclude that satellite DNA hypomethylation is an important issue in ovarian carcinogenesis as demonstrated by: (a) an increase from non-neoplastic tissue toward ovarian cancer; (b) an increase within the ovarian cancer group toward advanced grade and stage; and (c) the finding that strong hypomethylation was an independent marker of poor prognosis.
Data from Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice
Authors: Felix Klaus , Polack Axel , Pretsch Walter , Jackson Sharon H. , Feigenbaum Lionel , Bornkamm Georg-Wilhelm , Janz Siegfried
Published: March 2023

Abstract
Mutator phenotypes, a common and largely unexplained attribute of human cancer, might be better understood in mouse tumors containing reporter genes for accurate mutation enumeration and analysis. Previous work on peritoneal plasmacytomas (PCTs) in mice suggested that PCTs have a mutator phenotype caused by Myc-deregulating chromosomal translocations and/or phagocyte-induced mutagenesis due to chronic inflammation. To investigate this hypothesis, we generated PCTs that harbored the transgenic shuttle vector, pUR288, with a lacZ reporter gene for the assessment of mutations in vivo. PCTs exhibited a 5.5 times higher mutant frequency in lacZ (40.3 ± 5.1 × 10−5) than in normal B cells (7.36 ± 0.77 × 10−5), demonstrating that the tumors exhibit the phenotype of increased mutability. Studies on lacZ mutant frequency in serially transplanted PCTs and phagocyte-induced lacZ mutations in B cells in vitro indicated that mutant levels in tumors are not determined by exogenous damage inflicted by inflammatory cells. In vitro studies with a newly developed transgenic model of inducible Myc expression (Tet-off/MYC) showed that deregulated Myc sensitizes B cells to chemically induced mutations, but does not cause, on its own, mutations in lacZ. These findings suggested that the hypermutability of PCT is governed mainly by intrinsic features of tumor cells, not by deregulated Myc or chronic inflammation.