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768 results on '"Flanagan, Adrienne M."'

1. OMG-Net: A Deep Learning Framework Deploying Segment Anything to Detect Pan-Cancer Mitotic Figures from Haematoxylin and Eosin-Stained Slides

Author

Shen, Zhuoyan, Simard, Mikael, Brand, Douglas, Andrei, Vanghelita, Al-Khader, Ali, Oumlil, Fatine, Trevers, Katherine, Butters, Thomas, Haefliger, Simon, Kara, Eleanna, Amary, Fernanda, Tirabosco, Roberto, Cool, Paul, Royle, Gary, Hawkins, Maria A., Flanagan, Adrienne M., and Fekete, Charles-Antoine Collins

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Mitotic activity is an important feature for grading several cancer types. Counting mitotic figures (MFs) is a time-consuming, laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment. In this study, we propose an artificial intelligence (AI)-aided approach to detect MFs in digitised haematoxylin and eosin-stained whole slide images (WSIs). Advances in this area are hampered by the limited number and types of cancer datasets of MFs. Here we establish the largest pan-cancer dataset of mitotic figures by combining an in-house dataset of soft tissue tumours (STMF) with five open-source mitotic datasets comprising multiple human cancers and canine specimens (ICPR, TUPAC, CCMCT, CMC and MIDOG++). This new dataset identifies 74,620 MFs and 105,538 mitotic-like figures. We then employed a two-stage framework (the Optimised Mitoses Generator Network (OMG-Net) to classify MFs. The framework first deploys the Segment Anything Model (SAM) to automate the contouring of MFs and surrounding objects. An adapted ResNet18 is subsequently trained to classify MFs. OMG-Net reaches an F1-score of 0.84 on pan-cancer MF detection (breast carcinoma, neuroendocrine tumour and melanoma), largely outperforming the previous state-of-the-art MIDOG++ benchmark model on its hold-out testing set (e.g. +16% F1-score on breast cancer detection, p<0.001) thereby providing superior accuracy in detecting MFs on various types of tumours obtained with different scanners.

Published
2024

4. Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

Author

Gianferante, D. Matthew, Moore, Amy, Spector, Logan G., Wheeler, William, Yang, Tianzhong, Hubbard, Aubrey, Gorlick, Richard, Patiño-Garcia, Ana, Lecanda, Fernando, Flanagan, Adrienne M., Amary, Fernanda, Andrulis, Irene L., Wunder, Jay S., Thomas, David M., Ballinger, Mandy L., Serra, Massimo, Hattinger, Claudia, Demerath, Ellen, Johnson, Will, Birmann, Brenda M., De Vivo, Immaculata, Giles, Graham, Teras, Lauren R., Arslan, Alan, Vermeulen, Roel, Sample, Jeannette, Freedman, Neal D., Huang, Wen-Yi, Chanock, Stephen J., Savage, Sharon A., Berndt, Sonja I., and Mirabello, Lisa

Published
2024
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5. Diagnostic classification of childhood cancer using multiscale transcriptomics

Author

Comitani, Federico, Nash, Joshua O., Cohen-Gogo, Sarah, Chang, Astra I., Wen, Timmy T., Maheshwari, Anant, Goyal, Bipasha, Tio, Earvin S., Tabatabaei, Kevin, Mayoh, Chelsea, Zhao, Regis, Ho, Ben, Brunga, Ledia, Lawrence, John E. G., Balogh, Petra, Flanagan, Adrienne M., Teichmann, Sarah, Huang, Annie, Ramaswamy, Vijay, Hitzler, Johann, Wasserman, Jonathan D., Gladdy, Rebecca A., Dickson, Brendan C., Tabori, Uri, Cowley, Mark J., Behjati, Sam, Malkin, David, Villani, Anita, Irwin, Meredith S., and Shlien, Adam

Published
2023
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6. Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma

Author

Beird, Hannah C., Wu, Chia-Chin, Nakazawa, Michael, Ingram, Davis, Daniele, Joseph R., Lazcano, Rossana, Little, Latasha, Davies, Christopher, Daw, Najat C., Wani, Khalida, Wang, Wei-Lien, Song, Xingzhi, Gumbs, Curtis, Zhang, Jianhua, Rubin, Brian, Conley, Anthony, Flanagan, Adrienne M., Lazar, Alexander J., and Futreal, P. Andrew

Published
2023
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7. Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone

Author

Cottone, Lucia, Ligammari, Lorena, Lee, Hang-Mao, Knowles, Helen J., Henderson, Stephen, Bianco, Sara, Davies, Christopher, Strauss, Sandra, Amary, Fernanda, Leite, Ana Paula, Tirabosco, Roberto, Haendler, Kristian, Schultze, Joachim L., Herrero, Javier, O’Donnell, Paul, Grigoriadis, Agamemnon E., Salomoni, Paolo, and Flanagan, Adrienne M.

Published
2022
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8. Signatures of copy number alterations in human cancer

Author

Steele, Christopher D., Abbasi, Ammal, Islam, S. M. Ashiqul, Bowes, Amy L., Khandekar, Azhar, Haase, Kerstin, Hames-Fathi, Shadi, Ajayi, Dolapo, Verfaillie, Annelien, Dhami, Pawan, McLatchie, Alex, Lechner, Matt, Light, Nicholas, Shlien, Adam, Malkin, David, Feber, Andrew, Proszek, Paula, Lesluyes, Tom, Mertens, Fredrik, Flanagan, Adrienne M., Tarabichi, Maxime, Van Loo, Peter, Alexandrov, Ludmil B., and Pillay, Nischalan

Published
2022
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10. Chromosome segregation errors generate a diverse spectrum of simple and complex genomic rearrangements.

Author

Ly, Peter, Brunner, Simon F, Shoshani, Ofer, Kim, Dong Hyun, Lan, Weijie, Pyntikova, Tatyana, Flanagan, Adrienne M, Behjati, Sam, Page, David C, Campbell, Peter J, and Cleveland, Don W

Subjects
Cells, Cultured, Animals, Xenopus laevis, Humans, Neoplasms, Chromosome Aberrations, Translocation, Genetic, Genomics, Chromosome Segregation, Gene Rearrangement, Genome, Human, DNA Copy Number Variations, HEK293 Cells, Whole Genome Sequencing, Cells, Cultured, Translocation, Genetic, Genome, Human, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Cancer genomes are frequently characterized by numerical and structural chromosomal abnormalities. Here we integrated a centromere-specific inactivation approach with selection for a conditionally essential gene, a strategy termed CEN-SELECT, to systematically interrogate the structural landscape of mis-segregated chromosomes. We show that single-chromosome mis-segregation into a micronucleus can directly trigger a broad spectrum of genomic rearrangement types. Cytogenetic profiling revealed that mis-segregated chromosomes exhibit 120-fold-higher susceptibility to developing seven major categories of structural aberrations, including translocations, insertions, deletions, and complex reassembly through chromothripsis coupled to classical non-homologous end joining. Whole-genome sequencing of clonally propagated rearrangements identified random patterns of clustered breakpoints with copy-number alterations resulting in interspersed gene deletions and extrachromosomal DNA amplification events. We conclude that individual chromosome segregation errors during mitotic cell division are sufficient to drive extensive structural variations that recapitulate genomic features commonly associated with human disease.

Published
2019

12. A genetic model for central chondrosarcoma evolution correlates with patient outcome

Author

Cross, William, Lyskjær, Iben, Lesluyes, Tom, Hargreaves, Steven, Strobl, Anna-Christina, Davies, Christopher, Waise, Sara, Hames-Fathi, Shadi, Oukrif, Dahmane, Ye, Hongtao, Amary, Fernanda, Tirabosco, Roberto, Gerrand, Craig, Baker, Toby, Barnes, David, Steele, Christopher, Alexandrov, Ludmil, Bond, Gareth, Cool, Paul, Pillay, Nischalan, Loo, Peter Van, and Flanagan, Adrienne M.

Published
2022
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13. Author Correction: Osteosarcoma

Author

Beird, Hannah C., Bielack, Stefan S., Flanagan, Adrienne M., Gill, Jonathan, Heymann, Dominique, Janeway, Katherine A., Livingston, J. Andrew, Roberts, Ryan D., Strauss, Sandra J., and Gorlick, Richard

Published
2022
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21. The driver landscape of sporadic chordoma.

Author

Tarpey, Patrick S, Behjati, Sam, Young, Matthew D, Martincorena, Inigo, Alexandrov, Ludmil B, Farndon, Sarah J, Guzzo, Charlotte, Hardy, Claire, Latimer, Calli, Butler, Adam P, Teague, Jon W, Shlien, Adam, Futreal, P Andrew, Shah, Sohrab, Bashashati, Ali, Jamshidi, Farzad, Nielsen, Torsten O, Huntsman, David, Baumhoer, Daniel, Brandner, Sebastian, Wunder, Jay, Dickson, Brendan, Cogswell, Patricia, Sommer, Josh, Phillips, Joanna J, Amary, M Fernanda, Tirabosco, Roberto, Pillay, Nischalan, Yip, Stephen, Stratton, Michael R, Flanagan, Adrienne M, and Campbell, Peter J

Subjects
Cell Line, Tumor, Humans, Chordoma, Bone Neoplasms, T-Box Domain Proteins, Fetal Proteins, Vesicular Transport Proteins, Case-Control Studies, Gene Duplication, Mutation, Polymorphism, Single Nucleotide, Phosphatidylinositol 3-Kinases, Class I Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Polymorphism, Single Nucleotide
Abstract

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

Published
2017

22. Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement

Author

Onderzoek Beeld, Green, Darrell, van Ewijk, Roelof, Tirtei, Elisa, Andreou, Dimosthenis, Baecklund, Fredrik, Baumhoer, Daniel, Bielack, Stefan S., Botchu, Rajesh, Boye, Kjetil, Brennan, Bernadette, Capra, Michael, Cottone, Lucia, Dirksen, Uta, Fagioli, Franca, Fernandez, Natalia, Flanagan, Adrienne M., Gambarotti, Marco, Gaspar, Nathalie, Gelderblom, Hans, Gerrand, Craig, Gomez-Mascard, Anne, Hardes, Jendrik, Hecker-Nolting, Stefanie, Kabickova, Edita, Kager, Leo, Kanerva, Jukka, Kester, Lennart A., Kuijjer, Marieke L., Laurence, Valérie, Lervat, Cyril, Marchais, Antonin, Marec-Berard, Perrine, Mendes, Cristina, Merks, Johannes H.M., Ory, Benjamin, Palmerini, Emanuela, Pantziarka, Pan, Papakonstantinou, Evgenia, Piperno-Neumann, Sophie, Raciborska, Anna, Roundhill, Elizabeth A., Rutkauskaite, Vilma, Safwat, Akmal, Scotlandi, Katia, Staals, Eric L., Strauss, Sandra J., Surdez, Didier, Sys, Gwen M.L., Tabone, Marie Dominique, Toulmonde, Maud, Valverde, Claudia, van de Sande, Michiel A.J., Wörtler, Klaus, Campbell-Hewson, Quentin, McCabe, Martin G., Nathrath, Michaela, Onderzoek Beeld, Green, Darrell, van Ewijk, Roelof, Tirtei, Elisa, Andreou, Dimosthenis, Baecklund, Fredrik, Baumhoer, Daniel, Bielack, Stefan S., Botchu, Rajesh, Boye, Kjetil, Brennan, Bernadette, Capra, Michael, Cottone, Lucia, Dirksen, Uta, Fagioli, Franca, Fernandez, Natalia, Flanagan, Adrienne M., Gambarotti, Marco, Gaspar, Nathalie, Gelderblom, Hans, Gerrand, Craig, Gomez-Mascard, Anne, Hardes, Jendrik, Hecker-Nolting, Stefanie, Kabickova, Edita, Kager, Leo, Kanerva, Jukka, Kester, Lennart A., Kuijjer, Marieke L., Laurence, Valérie, Lervat, Cyril, Marchais, Antonin, Marec-Berard, Perrine, Mendes, Cristina, Merks, Johannes H.M., Ory, Benjamin, Palmerini, Emanuela, Pantziarka, Pan, Papakonstantinou, Evgenia, Piperno-Neumann, Sophie, Raciborska, Anna, Roundhill, Elizabeth A., Rutkauskaite, Vilma, Safwat, Akmal, Scotlandi, Katia, Staals, Eric L., Strauss, Sandra J., Surdez, Didier, Sys, Gwen M.L., Tabone, Marie Dominique, Toulmonde, Maud, Valverde, Claudia, van de Sande, Michiel A.J., Wörtler, Klaus, Campbell-Hewson, Quentin, McCabe, Martin G., and Nathrath, Michaela

Published
2024

23. The history of chromosomal instability in genome doubled tumors

Author

Baker, Toby M., Lai, Siqi, Lynch, Andrew R., Lesluyes, Tom, Yan, Haixi, Ogilvie, Huw, Verfaillie, Annelien, Dentro, Stefan, Bowes, Amy L., Pillay, Nischalan, Flanagan, Adrienne M., Swanton, Charles, Spellman, Paul T, Tarabichi, Maxime, Van Loo, Peter, Baker, Toby M., Lai, Siqi, Lynch, Andrew R., Lesluyes, Tom, Yan, Haixi, Ogilvie, Huw, Verfaillie, Annelien, Dentro, Stefan, Bowes, Amy L., Pillay, Nischalan, Flanagan, Adrienne M., Swanton, Charles, Spellman, Paul T, Tarabichi, Maxime, and Van Loo, Peter

Abstract

Tumors frequently display high chromosomal instability and contain multiple copies of genomic regions. Here, we describe GRITIC, a generic method for timing genomic gains leading to complex copy number states, using single-sample bulk whole-genome sequencing data. By applying GRITIC to 6,091 tumors, we found that non-parsimonious evolution is frequent in the formation of complex copy number states in genome-doubled tumors. We measured chromosomal instability before and after genome duplication in human tumors and found that late genome doubling was followed by an increase in the rate of copy number gain. Copy number gains often accumulate as punctuated bursts, commonly after genome doubling. We infer that genome duplications typically affect the landscape of copy number losses, while only minimally impacting copy number gains. In summary, GRITIC is a novel copy number gain timing framework that permits the analysis of copy number evolution in chromosomally unstable tumors., info:eu-repo/semantics/published

Published
2024

24. Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

Author

Planetary Health & Exposoom, Cancer, Circulatory Health, Gianferante, D. Matthew, Moore, Amy, Spector, Logan G., Wheeler, William, Yang, Tianzhong, Hubbard, Aubrey, Gorlick, Richard, Patiño-Garcia, Ana, Lecanda, Fernando, Flanagan, Adrienne M., Amary, Fernanda, Andrulis, Irene L., Wunder, Jay S., Thomas, David M., Ballinger, Mandy L., Serra, Massimo, Hattinger, Claudia, Demerath, Ellen, Johnson, Will, Birmann, Brenda M., De Vivo, Immaculata, Giles, Graham, Teras, Lauren R., Arslan, Alan, Vermeulen, Roel, Sample, Jeannette, Freedman, Neal D., Huang, Wen Yi, Chanock, Stephen J., Savage, Sharon A., Berndt, Sonja I., Mirabello, Lisa, Planetary Health & Exposoom, Cancer, Circulatory Health, Gianferante, D. Matthew, Moore, Amy, Spector, Logan G., Wheeler, William, Yang, Tianzhong, Hubbard, Aubrey, Gorlick, Richard, Patiño-Garcia, Ana, Lecanda, Fernando, Flanagan, Adrienne M., Amary, Fernanda, Andrulis, Irene L., Wunder, Jay S., Thomas, David M., Ballinger, Mandy L., Serra, Massimo, Hattinger, Claudia, Demerath, Ellen, Johnson, Will, Birmann, Brenda M., De Vivo, Immaculata, Giles, Graham, Teras, Lauren R., Arslan, Alan, Vermeulen, Roel, Sample, Jeannette, Freedman, Neal D., Huang, Wen Yi, Chanock, Stephen J., Savage, Sharon A., Berndt, Sonja I., and Mirabello, Lisa

Published
2024

25. A Prospective Observational Cohort Study for Newly Diagnosed Osteosarcoma Patients in the UK: ICONIC Study Initial Results.

Author

Childs, Alexa, Gerrand, Craig, Brennan, Bernadette, Young, Robin, Rankin, Kenneth S., Parry, Michael, Stevenson, Jonathan, Flanagan, Adrienne M., Taylor, Rachel M., Fern, Lorna, Heymann, Dominique, Vance, Filipa, Sherriff, Jenny, Singh, Saurabh, Begum, Rubina, Forsyth, Sharon L., Reczko, Krystyna, Sparksman, Kate, Wilson, William, and Strauss, Sandra J.

Subjects
OSTEOSARCOMA, RESEARCH funding, HUMAN beings, SCIENTIFIC observation, CANCER patients, TUMOR markers, LONGITUDINAL method, QUALITY of life, HEALTH outcome assessment, COLLECTION & preservation of biological specimens
Abstract

Simple Summary: Treatment for osteosarcoma (OS) has remained largely unchanged over the past 25 years. This is due in part to the low incidence of the disease, which makes the design of and recruitment to clinical trials challenging. The aim of our ongoing study is to establish a platform for the recruitment of newly diagnosed OS patients across the UK, with corresponding collection of clinical and patient-reported outcome (PRO) data, as well as biospecimen sample collection. In Stage 1 of the study, we established the feasibility of patient recruitment and patient data and sample collection. In Stage 2, biological and clinical data will be correlated with outcomes to develop prognostic biomarkers and inform the development of future clinical trials. There has been little change to the standard treatment for osteosarcoma (OS) over the last 25 years and there is an unmet need to identify new biomarkers and novel therapeutic approaches if outcomes are to improve. Furthermore, there is limited evidence on the impact of OS treatment on patient-reported outcomes (PROs). ICONIC (Improving Outcomes through Collaboration in Osteosarcoma; NCT04132895) is a prospective observational cohort study recruiting newly diagnosed OS patients across the United Kingdom (UK) with matched longitudinal collection of clinical, biological, and PRO data. During Stage 1, which assessed the feasibility of recruitment and data collection, 102 patients were recruited at 22 sites with representation from patient groups frequently excluded in OS studies, including patients over 50 years and those with less common primary sites. The feasibility of collecting clinical and biological samples, in addition to PRO data, has been established and there is ongoing analysis of these data as part of Stage 2. ICONIC will provide a unique, prospective cohort of newly diagnosed OS patients representative of the UK patient population, with fully annotated clinical outcomes linked to molecularly characterised biospecimens, allowing for comprehensive analyses to better understand biology and develop new biomarkers and novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Single cell transcriptomics reveals chondrocyte differentiation dynamics in vivo and in vitro

Author

Lawrence, John E G, primary, Woods, Steven, additional, Roberts, Kenny, additional, Sumanaweera, Dinithi N, additional, Balogh, Petra, additional, Predeus, Alexander V, additional, He, Peng, additional, Li, Tong, additional, Polanski, Krzysztof, additional, Prigmore, Elena, additional, Tuck, Elizabeth, additional, Mamanova, Lira, additional, Zhou, Di, additional, Webb, Simone, additional, Jardine, Laura, additional, He, Xiaoling, additional, Barker, Roger A, additional, Haniffa, Muzlifah, additional, Flanagan, Adrienne M, additional, Young, Matthew D, additional, Behjati, Sam, additional, Bayraktar, Omer, additional, Kimber, Susan J, additional, and Teichmann, Sarah, additional

Published
2023
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30. Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

Author

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

Subjects
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.

Published
2015

31. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Wang, Zhaoming, Zhu, Bin, Zhang, Mingfeng, Parikh, Hemang, Jia, Jinping, Chung, Charles C, Sampson, Joshua N, Hoskins, Jason W, Hutchinson, Amy, Burdette, Laurie, Ibrahim, Abdisamad, Hautman, Christopher, Raj, Preethi S, Abnet, Christian C, Adjei, Andrew A, Ahlbom, Anders, Albanes, Demetrius, Allen, Naomi E, Ambrosone, Christine B, Aldrich, Melinda, Amiano, Pilar, Amos, Christopher, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Arici, Cecilia, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Beane Freeman, Laura E, Berg, Christine D, Berndt, Sonja I, Bertazzi, Pier Alberto, Biritwum, Richard B, Black, Amanda, Blot, William, Boeing, Heiner, Boffetta, Paolo, Bolton, Kelly, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brennan, Paul, Brinton, Louise A, Brotzman, Michelle, Bueno-de-Mesquita, H Bas, Buring, Julie E, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Cao, Guangwen, Caporaso, Neil E, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chang, Gee-Chen, Chang, I-Shou, Chang-Claude, Jenny, Che, Xu, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chung-Hsing, Chen, Constance, Chen, Kuan-Yu, Chen, Yuh-Min, Chokkalingam, Anand P, Chu, Lisa W, Clavel-Chapelon, Francoise, Colditz, Graham A, Colt, Joanne S, Conti, David, Cook, Michael B, Cortessis, Victoria K, Crawford, E David, Cussenot, Olivier, Davis, Faith G, De Vivo, Immaculata, Deng, Xiang, Ding, Ti, Dinney, Colin P, Di Stefano, Anna Luisa, Diver, W Ryan, Duell, Eric J, Elena, Joanne W, Fan, Jin-Hu, Feigelson, Heather Spencer, Feychting, Maria, Figueroa, Jonine D, Flanagan, Adrienne M, Fraumeni, Joseph F, Freedman, Neal D, Fridley, Brooke L, Fuchs, Charles S, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, and Garcia-Closas, Montserrat

Subjects
Biological Sciences, Genetics, Cancer, Clinical Research, Human Genome, Prevention, Aetiology, 2.1 Biological and endogenous factors, Alleles, Chromosomes, Human, Pair 5, Computational Biology, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Neoplasm Proteins, Neoplasms, Odds Ratio, Polymorphism, Single Nucleotide, Risk, Telomerase, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

33. The history of chromosomal instability in genome doubled tumors

Author

Baker, Toby M., primary, Lai, Siqi, additional, Lesluyes, Tom, additional, Yan, Haixi, additional, Verfaillie, Annelien, additional, Dentro, Stefan, additional, Lynch, Andrew R., additional, Bowes, Amy L., additional, Pillay, Nischalan, additional, Flanagan, Adrienne M., additional, Swanton, Charles, additional, Tarabichi, Maxime, additional, and Loo, Peter Van, additional

Published
2023
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35. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors

Author

Anderson, Nathaniel D., de Borja, Richard, Young, Matthew D., Fuligni, Fabio, Rosic, Andrej, Roberts, Nicola D., Hajjar, Simon, Layeghifard, Mehdi, Novokmet, Ana, Kowalski, Paul E., Anaka, Matthew, Davidson, Scott, Zarrei, Mehdi, Said, Badr Id, Schreiner, L. Christine, Marchand, Remi, Sitter, Joseph, Gokgoz, Nalan, Brunga, Ledia, Graham, Garrett T., Fullam, Anthony, Pillay, Nischalan, Toretsky, Jeffrey A., Yoshida, Akihiko, Shibata, Tatsuhiro, Metzler, Markus, Somers, Gino R., Scherer, Stephen W., Flanagan, Adrienne M., Campbell, Peter J., Schiffman, Joshua D., Shago, Mary, Alexandrov, Ludmil B., Wunder, Jay S., Andrulis, Irene L., Malkin, David, Behjati, Sam, and Shlien, Adam

Published
2018

37. Genetically inferred birthweight, height, and puberty timing and risk of osteosarcoma

Author

Gianferante, D. Matthew, primary, Moore, Amy, additional, Spector, Logan G., additional, Wheeler, William, additional, Yang, Tianzhong, additional, Hubbard, Aubrey, additional, Gorlick, Richard, additional, Patiño-Garcia, Ana, additional, Lecanda, Fernando, additional, Flanagan, Adrienne M., additional, Amary, Fernanda, additional, Andrulis, Irene L., additional, Wunder, Jay S., additional, Thomas, David M., additional, Ballinger, Mandy L., additional, Serra, Massimo, additional, Hattinger, Claudia, additional, Demerath, Ellen, additional, Johnson, Will, additional, Birmann, Brenda M., additional, De Vivo, Immaculata, additional, Giles, Graham, additional, Teras, Lauren R., additional, Arslan, Alan, additional, Vermeulen, Roel, additional, Sample, Jeannette, additional, Freedman, Neal D., additional, Huang, Wen-Yi, additional, Chanock, Stephen J., additional, Savage, Sharon A., additional, Berndt, Sonja I., additional, and Mirabello, Lisa, additional

Published
2023
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38. Subclassification of epithelioid sarcoma with potential therapeutic impact

Author

Haefliger, Simon, primary, Chervova, Olga, additional, Davies, Christopher, additional, Nottley, Steven, additional, Hargreaves, Steven, additional, Sumathi, Vaiyapuri P, additional, Amary, Fernanda, additional, Tirabosco, Roberto, additional, Pillay, Nischalan, additional, Beck, Stephan, additional, Flanagan, Adrienne M, additional, and Lyskjær, Iben, additional

Published
2023
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44. Data from Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA

Author

Cortes-Ciriano, Isidro, primary, Steele, Christopher D., primary, Piculell, Katherine, primary, Al-Ibraheemi, Alyaa, primary, Eulo, Vanessa, primary, Bui, Marilyn M., primary, Chatzipli, Aikaterini, primary, Dickson, Brendan C., primary, Borcherding, Dana C., primary, Feber, Andrew, primary, Galor, Alon, primary, Hart, Jesse, primary, Jones, Kevin B., primary, Jordan, Justin T., primary, Kim, Raymond H., primary, Lindsay, Daniel, primary, Miller, Colin, primary, Nishida, Yoshihiro, primary, Proszek, Paula Z., primary, Serrano, Jonathan, primary, Sundby, R. Taylor, primary, Szymanski, Jeffrey J., primary, Ullrich, Nicole J., primary, Viskochil, David, primary, Wang, Xia, primary, Snuderl, Matija, primary, Park, Peter J., primary, Flanagan, Adrienne M., primary, Hirbe, Angela C., primary, Pillay, Nischalan, primary, and Miller, David T., primary

Published
2023
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45. Supplementary Figures 1-15 from Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA

Author

Cortes-Ciriano, Isidro, primary, Steele, Christopher D., primary, Piculell, Katherine, primary, Al-Ibraheemi, Alyaa, primary, Eulo, Vanessa, primary, Bui, Marilyn M., primary, Chatzipli, Aikaterini, primary, Dickson, Brendan C., primary, Borcherding, Dana C., primary, Feber, Andrew, primary, Galor, Alon, primary, Hart, Jesse, primary, Jones, Kevin B., primary, Jordan, Justin T., primary, Kim, Raymond H., primary, Lindsay, Daniel, primary, Miller, Colin, primary, Nishida, Yoshihiro, primary, Proszek, Paula Z., primary, Serrano, Jonathan, primary, Sundby, R. Taylor, primary, Szymanski, Jeffrey J., primary, Ullrich, Nicole J., primary, Viskochil, David, primary, Wang, Xia, primary, Snuderl, Matija, primary, Park, Peter J., primary, Flanagan, Adrienne M., primary, Hirbe, Angela C., primary, Pillay, Nischalan, primary, and Miller, David T., primary

Published
2023
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46. Supplementary Tables S1 and S2 from Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA

Author

Cortes-Ciriano, Isidro, primary, Steele, Christopher D., primary, Piculell, Katherine, primary, Al-Ibraheemi, Alyaa, primary, Eulo, Vanessa, primary, Bui, Marilyn M., primary, Chatzipli, Aikaterini, primary, Dickson, Brendan C., primary, Borcherding, Dana C., primary, Feber, Andrew, primary, Galor, Alon, primary, Hart, Jesse, primary, Jones, Kevin B., primary, Jordan, Justin T., primary, Kim, Raymond H., primary, Lindsay, Daniel, primary, Miller, Colin, primary, Nishida, Yoshihiro, primary, Proszek, Paula Z., primary, Serrano, Jonathan, primary, Sundby, R. Taylor, primary, Szymanski, Jeffrey J., primary, Ullrich, Nicole J., primary, Viskochil, David, primary, Wang, Xia, primary, Snuderl, Matija, primary, Park, Peter J., primary, Flanagan, Adrienne M., primary, Hirbe, Angela C., primary, Pillay, Nischalan, primary, and Miller, David T., primary

Published
2023
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47. Data from A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma

Author

Mirabello, Lisa, primary, Koster, Roelof, primary, Moriarity, Branden S., primary, Spector, Logan G., primary, Meltzer, Paul S., primary, Gary, Joy, primary, Machiela, Mitchell J., primary, Pankratz, Nathan, primary, Panagiotou, Orestis A., primary, Largaespada, David, primary, Wang, Zhaoming, primary, Gastier-Foster, Julie M., primary, Gorlick, Richard, primary, Khanna, Chand, primary, de Toledo, Silvia Regina Caminada, primary, Petrilli, Antonio S., primary, Patiño-Garcia, Ana, primary, Sierrasesúmaga, Luis, primary, Lecanda, Fernando, primary, Andrulis, Irene L., primary, Wunder, Jay S., primary, Gokgoz, Nalan, primary, Serra, Massimo, primary, Hattinger, Claudia, primary, Picci, Piero, primary, Scotlandi, Katia, primary, Flanagan, Adrienne M., primary, Tirabosco, Roberto, primary, Amary, Maria Fernanda, primary, Halai, Dina, primary, Ballinger, Mandy L., primary, Thomas, David M., primary, Davis, Sean, primary, Barkauskas, Donald A., primary, Marina, Neyssa, primary, Helman, Lee, primary, Otto, George M., primary, Becklin, Kelsie L., primary, Wolf, Natalie K., primary, Weg, Madison T., primary, Tucker, Margaret, primary, Wacholder, Sholom, primary, Fraumeni, Joseph F., primary, Caporaso, Neil E., primary, Boland, Joseph F., primary, Hicks, Belynda D., primary, Vogt, Aurelie, primary, Burdett, Laurie, primary, Yeager, Meredith, primary, Hoover, Robert N., primary, Chanock, Stephen J., primary, and Savage, Sharon A., primary

Published
2023
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48. Supplementary Table 3 from A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma

Author

Mirabello, Lisa, primary, Koster, Roelof, primary, Moriarity, Branden S., primary, Spector, Logan G., primary, Meltzer, Paul S., primary, Gary, Joy, primary, Machiela, Mitchell J., primary, Pankratz, Nathan, primary, Panagiotou, Orestis A., primary, Largaespada, David, primary, Wang, Zhaoming, primary, Gastier-Foster, Julie M., primary, Gorlick, Richard, primary, Khanna, Chand, primary, de Toledo, Silvia Regina Caminada, primary, Petrilli, Antonio S., primary, Patiño-Garcia, Ana, primary, Sierrasesúmaga, Luis, primary, Lecanda, Fernando, primary, Andrulis, Irene L., primary, Wunder, Jay S., primary, Gokgoz, Nalan, primary, Serra, Massimo, primary, Hattinger, Claudia, primary, Picci, Piero, primary, Scotlandi, Katia, primary, Flanagan, Adrienne M., primary, Tirabosco, Roberto, primary, Amary, Maria Fernanda, primary, Halai, Dina, primary, Ballinger, Mandy L., primary, Thomas, David M., primary, Davis, Sean, primary, Barkauskas, Donald A., primary, Marina, Neyssa, primary, Helman, Lee, primary, Otto, George M., primary, Becklin, Kelsie L., primary, Wolf, Natalie K., primary, Weg, Madison T., primary, Tucker, Margaret, primary, Wacholder, Sholom, primary, Fraumeni, Joseph F., primary, Caporaso, Neil E., primary, Boland, Joseph F., primary, Hicks, Belynda D., primary, Vogt, Aurelie, primary, Burdett, Laurie, primary, Yeager, Meredith, primary, Hoover, Robert N., primary, Chanock, Stephen J., primary, and Savage, Sharon A., primary

Published
2023
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49. Supplementary Table 1 from A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma

Author

Mirabello, Lisa, primary, Koster, Roelof, primary, Moriarity, Branden S., primary, Spector, Logan G., primary, Meltzer, Paul S., primary, Gary, Joy, primary, Machiela, Mitchell J., primary, Pankratz, Nathan, primary, Panagiotou, Orestis A., primary, Largaespada, David, primary, Wang, Zhaoming, primary, Gastier-Foster, Julie M., primary, Gorlick, Richard, primary, Khanna, Chand, primary, de Toledo, Silvia Regina Caminada, primary, Petrilli, Antonio S., primary, Patiño-Garcia, Ana, primary, Sierrasesúmaga, Luis, primary, Lecanda, Fernando, primary, Andrulis, Irene L., primary, Wunder, Jay S., primary, Gokgoz, Nalan, primary, Serra, Massimo, primary, Hattinger, Claudia, primary, Picci, Piero, primary, Scotlandi, Katia, primary, Flanagan, Adrienne M., primary, Tirabosco, Roberto, primary, Amary, Maria Fernanda, primary, Halai, Dina, primary, Ballinger, Mandy L., primary, Thomas, David M., primary, Davis, Sean, primary, Barkauskas, Donald A., primary, Marina, Neyssa, primary, Helman, Lee, primary, Otto, George M., primary, Becklin, Kelsie L., primary, Wolf, Natalie K., primary, Weg, Madison T., primary, Tucker, Margaret, primary, Wacholder, Sholom, primary, Fraumeni, Joseph F., primary, Caporaso, Neil E., primary, Boland, Joseph F., primary, Hicks, Belynda D., primary, Vogt, Aurelie, primary, Burdett, Laurie, primary, Yeager, Meredith, primary, Hoover, Robert N., primary, Chanock, Stephen J., primary, and Savage, Sharon A., primary

Published
2023
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50. Supplementary Table 6 from A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma

Author

Mirabello, Lisa, primary, Koster, Roelof, primary, Moriarity, Branden S., primary, Spector, Logan G., primary, Meltzer, Paul S., primary, Gary, Joy, primary, Machiela, Mitchell J., primary, Pankratz, Nathan, primary, Panagiotou, Orestis A., primary, Largaespada, David, primary, Wang, Zhaoming, primary, Gastier-Foster, Julie M., primary, Gorlick, Richard, primary, Khanna, Chand, primary, de Toledo, Silvia Regina Caminada, primary, Petrilli, Antonio S., primary, Patiño-Garcia, Ana, primary, Sierrasesúmaga, Luis, primary, Lecanda, Fernando, primary, Andrulis, Irene L., primary, Wunder, Jay S., primary, Gokgoz, Nalan, primary, Serra, Massimo, primary, Hattinger, Claudia, primary, Picci, Piero, primary, Scotlandi, Katia, primary, Flanagan, Adrienne M., primary, Tirabosco, Roberto, primary, Amary, Maria Fernanda, primary, Halai, Dina, primary, Ballinger, Mandy L., primary, Thomas, David M., primary, Davis, Sean, primary, Barkauskas, Donald A., primary, Marina, Neyssa, primary, Helman, Lee, primary, Otto, George M., primary, Becklin, Kelsie L., primary, Wolf, Natalie K., primary, Weg, Madison T., primary, Tucker, Margaret, primary, Wacholder, Sholom, primary, Fraumeni, Joseph F., primary, Caporaso, Neil E., primary, Boland, Joseph F., primary, Hicks, Belynda D., primary, Vogt, Aurelie, primary, Burdett, Laurie, primary, Yeager, Meredith, primary, Hoover, Robert N., primary, Chanock, Stephen J., primary, and Savage, Sharon A., primary

Published
2023
Full Text
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