841 results on '"Span, Paul N"'
Search Results
2. Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging
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Beerkens, Anne P. M., Boreel, Daan F., Nathan, James A., Neuzil, Jiri, Cheng, Gang, Kalyanaraman, Balaraman, Hardy, Micael, Adema, Gosse J., Heskamp, Sandra, Span, Paul N., and Bussink, Johan
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- 2024
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3. Inhibition of OXPHOS induces metabolic rewiring and reduces hypoxia in murine tumor models
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Boreel, Daan F., Beerkens, Anne P.M., Heskamp, Sandra, Boswinkel, Milou, Peters, Johannes P.W., Adema, Gosse J., Span, Paul N., and Bussink, Johan
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- 2024
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4. Combining immunotherapy and radiation therapy in gastrointestinal cancers: A review
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Mitrea, Diana A., Froicu, Eliza M., Prenen, Hans, Gambacorta, Maria A., Span, Paul N., and Poortmans, Philip
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- 2024
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5. Obesity-associated changes in molecular biology of primary breast cancer
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Nguyen, Ha-Linh, Geukens, Tatjana, Maetens, Marion, Aparicio, Samuel, Bassez, Ayse, Borg, Ake, Brock, Jane, Broeks, Annegien, Caldas, Carlos, Cardoso, Fatima, De Schepper, Maxim, Delorenzi, Mauro, Drukker, Caroline A., Glas, Annuska M., Green, Andrew R., Isnaldi, Edoardo, Eyfjörð, Jórunn, Khout, Hazem, Knappskog, Stian, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Martens, John W. M., McCart Reed, Amy E., Murphy, Leigh, Naulaerts, Stefan, Nik-Zainal, Serena, Nevelsteen, Ines, Neven, Patrick, Piccart, Martine, Poncet, Coralie, Punie, Kevin, Purdie, Colin, Rakha, Emad A., Richardson, Andrea, Rutgers, Emiel, Vincent-Salomon, Anne, Simpson, Peter T., Schmidt, Marjanka K., Sotiriou, Christos, Span, Paul N., Tan, Kiat Tee Benita, Thompson, Alastair, Tommasi, Stefania, Van Baelen, Karen, Van de Vijver, Marc, Van Laere, Steven, van’t Veer, Laura, Viale, Giuseppe, Viari, Alain, Vos, Hanne, Witteveen, Anke T., Wildiers, Hans, Floris, Giuseppe, Garg, Abhishek D., Smeets, Ann, Lambrechts, Diether, Biganzoli, Elia, Richard, François, and Desmedt, Christine
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- 2023
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6. Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer
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Bell, Emily S., Shah, Pragya, Zuela-Sopilniak, Noam, Kim, Dongsung, Varlet, Alice-Anais, Morival, Julien L. P., McGregor, Alexandra L., Isermann, Philipp, Davidson, Patricia M., Elacqua, Joshua J., Lakins, Jonathan N., Vahdat, Linda, Weaver, Valerie M., Smolka, Marcus B., Span, Paul N., and Lammerding, Jan
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- 2022
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7. Siglec‐7 and Siglec‐9 expression in primary triple negative and oestrogen receptor positive breast cancer and in vitro signalling.
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van Houtum, Eline JH, Valk, Anne HC, Granado, Daniel, Lok, Jasper, van den Bogaard, Lune, Remkes, Naomi, van Eck van der Sluijs, Jesper, Span, Paul N, Cornelissen, Lenneke AM, and Adema, Gosse J
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TRIPLE-negative breast cancer ,METASTATIC breast cancer ,CANCER patients ,MYELOID cells ,BREAST cancer - Abstract
Objectives: PD‐1/PD‐L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) breast tumors does not generate an effective immunotherapy response. Therefore, new treatment strategies have to be developed. Here, we investigate Siglec‐7 and Siglec‐9 as novel ITIM‐bearing inhibitory immune checkpoint receptors similar to PD‐1, but expressed on a broader range of immune cells. Methods: We assessed Siglec‐7 and Siglec‐9 (ligand) expression in TN and ER+ breast cancer tumors and their breast cancer cell line‐induced signalling. Results: We report that Siglec‐7 and Siglec‐9 are highly expressed in TN tumors, and to a low extent in ER+ tumors. Siglec‐7 was observed on myeloid cells, T cells, and NK cells and Siglec‐9 preferentially on myeloid cells. Expression of sialoglycans, including Siglec‐7 and Siglec‐9 ligands, was observed in both TN and ER+ breast cancer tissue sections. Expression levels of Siglec‐7 and Siglec‐9 ligands were higher on in vitro cultured TN cell lines than ER+ cell lines. Importantly, by applying chimeric Siglec‐7 reporter cells, we showed the induction of Siglec‐7 signalling by multiple TN cell lines, but only by one ER+ cell line. Moreover, Siglec‐7 signalling is directly related to Siglec‐7 ligand expression levels of breast cancer cell lines. Conclusion: These data imply that immunotherapy targeting Siglec receptors may be particularly interesting for TN breast cancer patients not responding to current treatment strategies with tumors displaying high immune cell infiltration. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo.
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Ju, Young Seok, Martincorena, Inigo, Gerstung, Moritz, Petljak, Mia, Alexandrov, Ludmil B, Rahbari, Raheleh, Wedge, David C, Davies, Helen R, Ramakrishna, Manasa, Fullam, Anthony, Martin, Sancha, Alder, Christopher, Patel, Nikita, Gamble, Steve, O'Meara, Sarah, Giri, Dilip D, Sauer, Torril, Pinder, Sarah E, Purdie, Colin A, Borg, Åke, Stunnenberg, Henk, van de Vijver, Marc, Tan, Benita KT, Caldas, Carlos, Tutt, Andrew, Ueno, Naoto T, van 't Veer, Laura J, Martens, John WM, Sotiriou, Christos, Knappskog, Stian, Span, Paul N, Lakhani, Sunil R, Eyfjörd, Jórunn Erla, Børresen-Dale, Anne-Lise, Richardson, Andrea, Thompson, Alastair M, Viari, Alain, Hurles, Matthew E, Nik-Zainal, Serena, Campbell, Peter J, and Stratton, Michael R
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Blood Cells ,Humans ,Mutagenesis ,Cell Lineage ,Embryonic Development ,Mutation ,Mosaicism ,Germ-Line Mutation ,Genome ,Human ,Adult ,Embryo ,Mammalian ,Mutation Rate ,Embryo ,Mammalian ,Genome ,Human ,General Science & Technology - Abstract
Somatic cells acquire mutations throughout the course of an individual's life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and their contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. This study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.
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- 2017
9. 46,XX males with congenital adrenal hyperplasia: a clinical and biochemical description.
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Adriaansen, Bas P. H., Utari, Agustini, Westra, Dineke, Juniarto, Achmad Zulfa, Ariani, Mahayu Dewi, Ediati, Annastasia, Schröder, Mariska A. M., Span, Paul N., Sweep, Fred C. G. J., Drop, Stenvert L. S., Faradz, Sultana M. H., van Herwaarden, Antonius E., and van der Grinten, Hedi L. Claahsen
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VULVA ,ADRENOGENITAL syndrome ,DELAYED diagnosis ,RENIN ,SYMPTOMS - Abstract
Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges. Methods: Nine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated. Results: All patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels. Discussion: We describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed. [ABSTRACT FROM AUTHOR]
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- 2024
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10. The tumor microenvironment and radiotherapy response; a central role for cancer-associated fibroblasts
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Ansems, Marleen and Span, Paul N.
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- 2020
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11. Reference intervals for serum 11-oxygenated androgens in children
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Adriaansen, Bas P H, primary, Oude Alink, Sandra E, additional, Swinkels, Dorine W, additional, Schröder, Mariska A M, additional, Span, Paul N, additional, Sweep, Fred C G J, additional, Claahsen-van der Grinten, Hedi L, additional, and van Herwaarden, Antonius E, additional
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- 2024
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12. Prognostic significance of VEGF and components of the plasminogen activator system in endometrial cancer
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Abbink, Karin, Zusterzeel, Petra L. M., Geurts-Moespot, Anneke, van der Steen, Rob, Span, Paul. N., and Sweep, Fred C. G. J.
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- 2020
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13. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells
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Ju, Young Seok, Tubio, Jose MC, Mifsud, William, Fu, Beiyuan, Davies, Helen R, Ramakrishna, Manasa, Li, Yilong, Yates, Lucy, Gundem, Gunes, Tarpey, Patrick S, Behjati, Sam, Papaemmanuil, Elli, Martin, Sancha, Fullam, Anthony, Gerstung, Moritz, Group, ICGC Prostate Cancer Working, Group, ICGC Bone Cancer Working, Group, ICGC Breast Cancer Working, Nangalia, Jyoti, Green, Anthony R, Caldas, Carlos, Borg, Åke, Tutt, Andrew, Lee, Ming Ta Michael, Veer, Laura J van't, Tan, Benita KT, Aparicio, Samuel, Span, Paul N, Martens, John WM, Knappskog, Stian, Vincent-Salomon, Anne, Børresen-Dale, Anne-Lise, Eyfjörd, Jórunn Erla, Flanagan, Adrienne M, Foster, Christopher, Neal, David E, Cooper, Colin, Eeles, Rosalind, Lakhani, Sunil R, Desmedt, Christine, Thomas, Gilles, Richardson, Andrea L, Purdie, Colin A, Thompson, Alastair M, McDermott, Ultan, Yang, Fengtang, Nik-Zainal, Serena, Campbell, Peter J, and Stratton, Michael R
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Biochemistry and Cell Biology ,Genetics ,Biological Sciences ,Stem Cell Research - Nonembryonic - Human ,Human Genome ,Stem Cell Research ,Cancer ,1.1 Normal biological development and functioning ,Underpinning research ,Aetiology ,2.1 Biological and endogenous factors ,Generic health relevance ,Amino Acid Sequence ,Cell Line ,Tumor ,Cell Nucleus ,Chromosomes ,DNA Copy Number Variations ,DNA End-Joining Repair ,DNA Replication ,DNA ,Mitochondrial ,Genome ,Human ,Genome ,Mitochondrial ,HeLa Cells ,Humans ,In Situ Hybridization ,Fluorescence ,Mitochondria ,Molecular Sequence Data ,Neoplasms ,Reproducibility of Results ,Sequence Analysis ,DNA ,ICGC Prostate Cancer Working Group ,ICGC Bone Cancer Working Group ,ICGC Breast Cancer Working Group ,Hela Cells ,Medical and Health Sciences ,Bioinformatics - Abstract
Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.
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- 2015
14. Inhibition of CDK4/CDK6 Enhances Radiosensitivity of HPV Negative Head and Neck Squamous Cell Carcinomas
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Göttgens, Eva-Leonne, Bussink, Johan, Leszczynska, Katarzyna B., Peters, Hans, Span, Paul N., and Hammond, Ester M.
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- 2019
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15. Evaluation of Ex Vivo Adrenocorticotropic Hormone Responsiveness of Human Fetal Testis
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Schröder, Mariska A M, primary, Greenald, David, additional, Lodewijk, Renate, additional, van Herwaarden, Antonius E, additional, Span, Paul N, additional, Sweep, Fred C G J, additional, Mitchell, Rod T, additional, and Claahsen-van der Grinten, Hedi L, additional
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- 2023
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16. Hormonal control during infancy and testicular adrenal rest tumor development in CAH males - a retrospective multi-center cohort study
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Schröder, Mariska A M, primary, Neacşu, Mihaela, additional, Adriaansen, Bas P H, additional, Sweep, Fred C G J, additional, Ahmed, S Faisal, additional, Ali, Salma R, additional, Bachega, Tânia A S S, additional, Baronio, Federico, additional, Birkebæk, Niels Holtum, additional, de Bruin, Christiaan, additional, Bonfig, Walter, additional, Bryce, Jillian, additional, Clemente, Maria, additional, Cools, Martine, additional, Elsedfy, Heba, additional, Globa, Evgenia, additional, Guran, Tulay, additional, Güven, Ayla, additional, Amr, Nermine Hussein, additional, Janus, Dominika, additional, Taube, Nina Lenherr, additional, Markosyan, Renata, additional, Miranda, Mirela, additional, Poyrazoğlu, Şükran, additional, Rees, Aled, additional, Salerno, Mariacarolina, additional, Stancampiano, Marianna Rita, additional, Vieites, Ana, additional, de Vries, Liat, additional, Yavas Abali, Zehra, additional, Span, Paul N, additional, and Claahsen-van der Grinten, Hedi L, additional
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- 2023
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17. 406: Radiotherapy induces an increase in serum antioxidant capacity reflecting tumor response
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Naumann, Flavia, Kaanders, Hans J.H.A.M., Peeters, Wenny W.J.M., Adema, Gosse J., Sweep, Fred C.G.J., Bussink, Jan, and Span, Paul N.
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- 2024
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18. 327: Inhibition of OXPHOS induces a metabolic switch and reduces hypoxia in immunocompetent tumor models
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Boreel, Daan F., Beerkens, Anne P.M., Span, Paul N., Peters, Johannes P.W., Boswinkel, Milou, Adema, Gosse J., Heskamp, Sandra, and Bussink, Johan
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- 2024
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19. Staining Against Phospho-H2AX (γ-H2AX) as a Marker for DNA Damage and Genomic Instability in Cancer Tissues and Cells
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Nagelkerke, Anika, Span, Paul N., Koumenis, Constantinos, editor, Coussens, Lisa M., editor, Giaccia, Amato, editor, and Hammond, Ester, editor
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- 2016
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20. Engineered microparticles delivering oxygen to enhance radiotherapy efficacy
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Span, Paul N., Bussink, Johan, and Kaanders, Johannes H. A. M.
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- 2016
21. Differential expression of p120-catenin 1 and 3 isoforms in epithelial tissues
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Venhuizen, Jan-Hendrik, Sommer, Sebastian, Span, Paul N., Friedl, Peter, and Zegers, Mirjam M.
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- 2019
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22. The association between hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia
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Schroder, Mariska, primary, Neacşu, Mihaela, additional, Sweep, Fred, additional, Span, Paul N, additional, Adriaansen, Bas, additional, van, Herwaarden Antonius, additional, Bryce, Jillian, additional, Ahmed, Faisal, additional, Ali, Salma, additional, Aparecida, Sartori Sanchez Bachega Tania, additional, Baronio, Federico, additional, Holtum, Birkebaek Niels, additional, Bonfig, Walter, additional, Clemente, Maria, additional, Cools, Martine, additional, de, Bruin Christiaan, additional, de, Vries Liat, additional, Elsedfy, Heba, additional, Globa, Evgenia, additional, Guran, Tulay, additional, Guven, Ayla, additional, Amr, Nermine Hussein, additional, Januś, Dominika, additional, Konrad, Daniel, additional, Markosyan, Renata, additional, Miranda, Mirela, additional, Poyrazoğlu, Şukran, additional, Rees, Aled, additional, Salerno, Mariacarolina, additional, Stancampiano, Marianna Rita, additional, Vieitis, Ana, additional, Abali, Zehra Yavas, additional, and -, van der Grinten Hedi Claahsen, additional
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- 2023
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23. Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase
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Roelofs, Pieter A., primary, Timmermans, Mieke A. M., additional, Stefanovska, Bojana, additional, den Boestert, Myrthe A., additional, van den Borne, Amber W. M., additional, Balcioglu, Hayri E., additional, Trapman, Anita M., additional, Harris, Reuben S., additional, Martens, John W. M., additional, and Span, Paul N., additional
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- 2023
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24. Supplementary Table S2 from Improved Recurrence-Free Survival with ARCON for Anemic Patients with Laryngeal Cancer
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Janssens, Geert O., primary, Rademakers, Saskia E., primary, Terhaard, Chris H., primary, Doornaert, Patricia A., primary, Bijl, Hendrik P., primary, van den Ende, Piet, primary, Chin, Alim, primary, Takes, Robert P., primary, de Bree, Remco, primary, Hoogsteen, Ilse J., primary, Bussink, Johan, primary, Span, Paul N., primary, and Kaanders, Johannes H., primary
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- 2023
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25. Table S1 from Interferon-Stimulated Genes Are Involved in Cross-resistance to Radiotherapy in Tamoxifen-Resistant Breast Cancer
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Post, Annemarie E.M., primary, Smid, Marcel, primary, Nagelkerke, Anika, primary, Martens, John W.M., primary, Bussink, Johan, primary, Sweep, Fred C.G.J., primary, and Span, Paul N., primary
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- 2023
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26. Supplementary data from A 26-Gene Hypoxia Signature Predicts Benefit from Hypoxia-Modifying Therapy in Laryngeal Cancer but Not Bladder Cancer
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Eustace, Amanda, primary, Mani, Navin, primary, Span, Paul N., primary, Irlam, Joely J., primary, Taylor, Janet, primary, Betts, Guy N.J., primary, Denley, Helen, primary, Miller, Crispin J., primary, Homer, Jarrod J., primary, Rojas, Ana M., primary, Hoskin, Peter J., primary, Buffa, Francesca M., primary, Harris, Adrian L., primary, Kaanders, Johannes H.A.M., primary, and West, Catharine M.L., primary
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- 2023
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27. Supplementary Tables and Figures from Hypoxic Activation of the PERK/eIF2α Arm of the Unfolded Protein Response Promotes Metastasis through Induction of LAMP3
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Mujcic, Hilda, primary, Nagelkerke, Anika, primary, Rouschop, Kasper M.A., primary, Chung, Stephen, primary, Chaudary, Naz, primary, Span, Paul N., primary, Clarke, Blaise, primary, Milosevic, Michael, primary, Sykes, Jenna, primary, Hill, Richard P., primary, Koritzinsky, Marianne, primary, and Wouters, Bradly G., primary
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- 2023
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28. Figure S3 from Interferon-Stimulated Genes Are Involved in Cross-resistance to Radiotherapy in Tamoxifen-Resistant Breast Cancer
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Post, Annemarie E.M., primary, Smid, Marcel, primary, Nagelkerke, Anika, primary, Martens, John W.M., primary, Bussink, Johan, primary, Sweep, Fred C.G.J., primary, and Span, Paul N., primary
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- 2023
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29. Supplementary Data from Hypoxic Activation of the PERK/eIF2α Arm of the Unfolded Protein Response Promotes Metastasis through Induction of LAMP3
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Mujcic, Hilda, primary, Nagelkerke, Anika, primary, Rouschop, Kasper M.A., primary, Chung, Stephen, primary, Chaudary, Naz, primary, Span, Paul N., primary, Clarke, Blaise, primary, Milosevic, Michael, primary, Sykes, Jenna, primary, Hill, Richard P., primary, Koritzinsky, Marianne, primary, and Wouters, Bradly G., primary
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- 2023
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30. Data from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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31. Supplementary Figure 3 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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32. Supplementary Figure 1 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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33. Supplementary Figure 4 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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34. Data from Matrix Metalloproteinase-8 Functions as a Metastasis Suppressor through Modulation of Tumor Cell Adhesion and Invasion
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Gutiérrez-Fernández, Ana, primary, Fueyo, Antonio, primary, Folgueras, Alicia R., primary, Garabaya, Cecilia, primary, Pennington, Caroline J., primary, Pilgrim, Simon, primary, Edwards, Dylan R., primary, Holliday, Deborah L., primary, Jones, J. Louise, primary, Span, Paul N., primary, Sweep, Fred C.G.J., primary, Puente, Xose S., primary, and López-Otín, Carlos, primary
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- 2023
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35. Supplementary Figure Legends 1-5 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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36. Supplementary Table 2 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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37. Supplementary Figure 1 from Matrix Metalloproteinase-8 Functions as a Metastasis Suppressor through Modulation of Tumor Cell Adhesion and Invasion
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Gutiérrez-Fernández, Ana, primary, Fueyo, Antonio, primary, Folgueras, Alicia R., primary, Garabaya, Cecilia, primary, Pennington, Caroline J., primary, Pilgrim, Simon, primary, Edwards, Dylan R., primary, Holliday, Deborah L., primary, Jones, J. Louise, primary, Span, Paul N., primary, Sweep, Fred C.G.J., primary, Puente, Xose S., primary, and López-Otín, Carlos, primary
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- 2023
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38. Supplementary Table 1 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
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- 2023
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39. Supplementary Figure 5 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
- Published
- 2023
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- View/download PDF
40. Supplementary Figure 2 from TRPM7 Is Required for Breast Tumor Cell Metastasis
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Middelbeek, Jeroen, primary, Kuipers, Arthur J., primary, Henneman, Linda, primary, Visser, Daan, primary, Eidhof, Ilse, primary, van Horssen, Remco, primary, Wieringa, Bé, primary, Canisius, Sander V., primary, Zwart, Wilbert, primary, Wessels, Lodewyk F., primary, Sweep, Fred C.G.J., primary, Bult, Peter, primary, Span, Paul N., primary, van Leeuwen, Frank N., primary, and Jalink, Kees, primary
- Published
- 2023
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- View/download PDF
41. Quantitative Imaging of Hypoxic CAIX-Positive Tumor Areas with Low Immune Cell Infiltration in Syngeneic Mouse Tumor Models
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Boreel, Daan F., primary, Span, Paul N., additional, Kip, Annemarie, additional, Boswinkel, Milou, additional, Peters, Johannes P. W., additional, Adema, Gosse J., additional, Bussink, Johan, additional, and Heskamp, Sandra, additional
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- 2023
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42. Obesity-associated changes in molecular biology of primary breast cancer.
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Nguyen, Ha Linh, Geukens, Tatjana, Maetens, Marion, Aparicio, Samuel, Bassez, Ayse, Borg, Åke A., Brock, Jane, Broeks, Annegien, Caldas, Carlos, Cardoso, Fatima, De Schepper, Maxim, Delorenzi, Mauro, Drukker, Caroline A, Glas, Annuska M, Green, Andrew R, Isnaldi, Edoardo, Eyfjörð, Jórunn, Khout, Hazem, Knappskog, Stian, Krishnamurthy, Savitri, Lakhani, Sunil R, Langerod, Anita, Martens, John W M, McCart Reed, Amy AE, Murphy, Leigh, Naulaerts, Stefan, Nik-Zainal, Serena, Nevelsteen, Ines, Neven, Patrick, Piccart, Martine, Poncet, Coralie, Punie, Kevin, Purdie, Colin, Rakha, Emad A, Richardson, Andrea, Rutgers, Emiel, Vincent-Salomon, Anne, Simpson, Peter T, Schmidt, Marjanka K, Sotiriou, Christos, Span, Paul N, Tan, Benita Kiat Tee BK, Thompson, Alastair, Tommasi, Stefania, Van Baelen, Karen, Van de Vijver, Marc, Van Laere, Steven, Van't Veer, Laura, Viale, Giuseppe, Viari, Alain, Vos, Hanne, Witteveen, Anke T, Wildiers, Hans, Floris, Giuseppe, Garg, Abhishek D, Smeets, Ann, Lambrechts, Diether, Biganzoli, Elia, Richard, François, Desmedt, Christine, Nguyen, Ha Linh, Geukens, Tatjana, Maetens, Marion, Aparicio, Samuel, Bassez, Ayse, Borg, Åke A., Brock, Jane, Broeks, Annegien, Caldas, Carlos, Cardoso, Fatima, De Schepper, Maxim, Delorenzi, Mauro, Drukker, Caroline A, Glas, Annuska M, Green, Andrew R, Isnaldi, Edoardo, Eyfjörð, Jórunn, Khout, Hazem, Knappskog, Stian, Krishnamurthy, Savitri, Lakhani, Sunil R, Langerod, Anita, Martens, John W M, McCart Reed, Amy AE, Murphy, Leigh, Naulaerts, Stefan, Nik-Zainal, Serena, Nevelsteen, Ines, Neven, Patrick, Piccart, Martine, Poncet, Coralie, Punie, Kevin, Purdie, Colin, Rakha, Emad A, Richardson, Andrea, Rutgers, Emiel, Vincent-Salomon, Anne, Simpson, Peter T, Schmidt, Marjanka K, Sotiriou, Christos, Span, Paul N, Tan, Benita Kiat Tee BK, Thompson, Alastair, Tommasi, Stefania, Van Baelen, Karen, Van de Vijver, Marc, Van Laere, Steven, Van't Veer, Laura, Viale, Giuseppe, Viari, Alain, Vos, Hanne, Witteveen, Anke T, Wildiers, Hans, Floris, Giuseppe, Garg, Abhishek D, Smeets, Ann, Lambrechts, Diether, Biganzoli, Elia, Richard, François, and Desmedt, Christine
- Abstract
Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients' body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2023
43. Quality-of-life after radiotherapy for advanced laryngeal cancer: Results of a phase III trial of the Dutch Head and Neck Society
- Author
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Janssens, Geert O., Langendijk, Johannes A., Terhaard, Chris H., Doornaert, Patricia A., van den Ende, Piet, de Jong, Martin A., Takes, Robert P., Span, Paul N., and Kaanders, Johannes H.
- Published
- 2016
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44. HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
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Halilovic, Altuna, Verweij, Dagmar I., Simons, Annet, Stevens-Kroef, Marian J. P. L., Vermeulen, Susan, Elsink, Janet, Tops, Bastiaan B. J., Otte-Höller, Irene, van der Laak, Jeroen A. W. M., van de Water, Carlijn, Boelens, Oliver B. A., Schlooz-Vries, Margrethe S., Dijkstra, Jeroen R., Nagtegaal, Iris D., Tol, Jolien, van Cleef, Patricia H. J., Span, Paul N., and Bult, Peter
- Published
- 2019
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45. Isocitrate dehydrogenase 1-mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate
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Peeters, Tom H., Lenting, Krissie, Breukels, Vincent, van Lith, Sanne A. M., van den Heuvel, Corina N. A. M., Molenaar, Remco, van Rooij, Arno, Wevers, Ron, Span, Paul N., Heerschap, Arend, and Leenders, William P. J.
- Published
- 2019
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46. Biology of Hypoxia
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Span, Paul N. and Bussink, Johan
- Published
- 2015
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47. Challenges in treatment of patients with non-classic congenital adrenal hyperplasia
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Adriaansen, Bas P. H., primary, Schröder, Mariska A. M., additional, Span, Paul N., additional, Sweep, Fred C. G. J., additional, van Herwaarden, Antonius E., additional, and Claahsen-van der Grinten, Hedi L., additional
- Published
- 2022
- Full Text
- View/download PDF
48. Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer
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Roelofs, Pieter A., primary, Martens, John W.M., additional, Harris, Reuben S., additional, and Span, Paul N., additional
- Published
- 2022
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- View/download PDF
49. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kellis, Manolis, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Khurana, Ekta, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong K, Kim, Youngwook, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komorowski, Jan, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korbel, Jan O, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Lanzós, Andrés, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lawrence, Michael S, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehmann, Kjong-Van, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lynch, Andy G, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Macintyre, Geoff, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin-Subero, Jose I, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, Mashl, R Jay, Massie, Charlie E, Matthew, Thomas J, Matthews, Lucy, Mayer, Erik, Mayes, Simon, Mayo, Michael, Mbabaali, Faridah, McCune, Karen, McDermott, Ultan, McGillivray, Patrick D, McLellan, Michael D, McPherson, John D, McPherson, John R, McPherson, Treasa A, Meier, Samuel R, Meng, Alice, Meng, Shaowu, Menzies, Andrew, Merrett, Neil D, Merson, Sue, Meyerson, Matthew, Meyerson, William, Mieczkowski, Piotr A, Mihaiescu, George L, Mijalkovic, Sanja, Mikkelsen, Tom, Milella, Michele, Mileshkin, Linda, Miller, Christopher A, Miller, David K, Miller, Jessica K, Mills, Gordon B, Milovanovic, Ana, Minner, Sarah, Miotto, Marco, Arnau, Gisela Mir, Mirabello, Lisa, Mitchell, Chris, Mitchell, Thomas J, Miyano, Satoru, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J, Mungall, 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Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
- Published
- 2023
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50. Combined burden and functional impact tests for cancer driver discovery using DriverPower
- Author
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- Subjects
Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
- Published
- 2023
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