192 results on '"Lee, Eunjung Alice"'
Search Results
2. Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication
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Hwang, Sung-Yeon, Kim, Hyewon, Denisko, Danielle, Zhao, Boxun, Lee, Dohoon, Jeong, Jiseok, Kim, Jinuk, Park, Kiwon, Park, Junhyun, Jeong, Dongjoon, Park, Sehong, Choi, Hee-Jung, Kim, Sun, Lee, Eunjung Alice, and Ahn, Kwangseog
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- 2024
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3. Analysis of REST binding sites with canonical and non-canonical motifs in human cell lines
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Choi, Jaejoon and Lee, Eunjung Alice
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- 2024
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4. Impaired neural stress resistance and loss of REST in bipolar disorder
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Meyer, Katharina, Ling, King-Hwa, Yeo, Pei-Ling, Spathopoulou, Angeliki, Drake, Derek, Choi, Jaejoon, Aron, Liviu, Garcia-Corral, Mariana, Ko, Tak, Lee, Eunjung Alice, Tam, Jenny M., Perlis, Roy H., Church, George M., Tsai, Li-Huei, and Yankner, Bruce A.
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- 2024
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5. A framework for individualized splice-switching oligonucleotide therapy
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Kim, Jinkuk, Woo, Sijae, de Gusmao, Claudio M., Zhao, Boxun, Chin, Diana H., DiDonato, Renata L., Nguyen, Minh A., Nakayama, Tojo, Hu, Chunguang April, Soucy, Aubrie, Kuniholm, Ashley, Thornton, Jennifer Karlin, Riccardi, Olivia, Friedman, Danielle A., El Achkar, Christelle Moufawad, Dash, Zane, Cornelissen, Laura, Donado, Carolina, Faour, Kamli N. W., Bush, Lynn W., Suslovitch, Victoria, Lentucci, Claudia, Park, Peter J., Lee, Eunjung Alice, Patterson, Al, Philippakis, Anthony A., Margus, Brad, Berde, Charles B., and Yu, Timothy W.
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- 2023
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6. ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia
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Lai, Jenny, Demirbas, Didem, Kim, Junho, Jeffries, Ailsa M., Tolles, Allie, Park, Junseok, Chittenden, Thomas W., Buckley, Patrick G., Yu, Timothy W., Lodato, Michael A., and Lee, Eunjung Alice
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- 2024
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7. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.
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Rodriguez-Martin, Bernardo, Alvarez, Eva G, Baez-Ortega, Adrian, Zamora, Jorge, Supek, Fran, Demeulemeester, Jonas, Santamarina, Martin, Ju, Young Seok, Temes, Javier, Garcia-Souto, Daniel, Detering, Harald, Li, Yilong, Rodriguez-Castro, Jorge, Dueso-Barroso, Ana, Bruzos, Alicia L, Dentro, Stefan C, Blanco, Miguel G, Contino, Gianmarco, Ardeljan, Daniel, Tojo, Marta, Roberts, Nicola D, Zumalave, Sonia, Edwards, Paul A, Weischenfeldt, Joachim, Puiggròs, Montserrat, Chong, Zechen, Chen, Ken, Lee, Eunjung Alice, Wala, Jeremiah A, Raine, Keiran M, Butler, Adam, Waszak, Sebastian M, Navarro, Fabio CP, Schumacher, Steven E, Monlong, Jean, Maura, Francesco, Bolli, Niccolo, Bourque, Guillaume, Gerstein, Mark, Park, Peter J, Wedge, David C, Beroukhim, Rameen, Torrents, David, Korbel, Jan O, Martincorena, Iñigo, Fitzgerald, Rebecca C, Van Loo, Peter, Kazazian, Haig H, Burns, Kathleen H, PCAWG Structural Variation Working Group, Campbell, Peter J, Tubio, Jose MC, and PCAWG Consortium
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PCAWG Structural Variation Working Group ,PCAWG Consortium ,Humans ,Neoplasms ,Retroelements ,Gene Rearrangement ,Long Interspersed Nucleotide Elements ,Genome ,Human ,Carcinogenesis ,Genetics ,Digestive Diseases ,Human Genome ,Cancer ,Rare Diseases ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
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- 2020
8. A neurodevelopmental disorder caused by a novel de novo SVA insertion in exon 13 of the SRCAP gene
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Zhao, Boxun, Madden, Jill A., Lin, Jasmine, Berry, Gerard T., Wojcik, Monica H., Zhao, Xuefang, Brand, Harrison, Talkowski, Michael, Lee, Eunjung Alice, and Agrawal, Pankaj B.
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- 2022
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9. Somatic mutations in single human cardiomyocytes reveal age-associated DNA damage and widespread oxidative genotoxicity
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Choudhury, Sangita, Huang, August Yue, Kim, Junho, Zhou, Zinan, Morillo, Katherine, Maury, Eduardo A., Tsai, Jessica W., Miller, Michael B., Lodato, Michael A., Araten, Sarah, Hilal, Nazia, Lee, Eunjung Alice, Chen, Ming Hui, and Walsh, Christopher A.
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- 2022
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10. Somatic genomic changes in single Alzheimer’s disease neurons
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Miller, Michael B., Huang, August Yue, Kim, Junho, Zhou, Zinan, Kirkham, Samantha L., Maury, Eduardo A., Ziegenfuss, Jennifer S., Reed, Hannah C., Neil, Jennifer E., Rento, Lariza, Ryu, Steven C., Ma, Chanthia C., Luquette, Lovelace J., Ames, Heather M., Oakley, Derek H., Frosch, Matthew P., Hyman, Bradley T., Lodato, Michael A., Lee, Eunjung Alice, and Walsh, Christopher A.
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- 2022
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11. Prevalence and mechanisms of somatic deletions in single human neurons during normal aging and in DNA repair disorders
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Kim, Junho, Huang, August Yue, Johnson, Shelby L., Lai, Jenny, Isacco, Laura, Jeffries, Ailsa M., Miller, Michael B., Lodato, Michael A., Walsh, Christopher A., and Lee, Eunjung Alice
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- 2022
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12. Author Correction: Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
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Rodriguez-Martin, Bernardo, Alvarez, Eva G., Baez-Ortega, Adrian, Zamora, Jorge, Supek, Fran, Demeulemeester, Jonas, Santamarina, Martin, Ju, Young Seok, Temes, Javier, Garcia-Souto, Daniel, Detering, Harald, Li, Yilong, Rodriguez-Castro, Jorge, Dueso-Barroso, Ana, Bruzos, Alicia L., Dentro, Stefan C., Blanco, Miguel G., Contino, Gianmarco, Ardeljan, Daniel, Tojo, Marta, Roberts, Nicola D., Zumalave, Sonia, Edwards, Paul A., Weischenfeldt, Joachim, Puiggròs, Montserrat, Chong, Zechen, Chen, Ken, Lee, Eunjung Alice, Wala, Jeremiah A., Raine, Keiran M., Butler, Adam, Waszak, Sebastian M., Navarro, Fabio C. P., Schumacher, Steven E., Monlong, Jean, Maura, Francesco, Bolli, Niccolo, Bourque, Guillaume, Gerstein, Mark, Park, Peter J., Wedge, David C., Beroukhim, Rameen, Torrents, David, Korbel, Jan O., Martincorena, Iñigo, Fitzgerald, Rebecca C., Van Loo, Peter, Kazazian, Haig H., Burns, Kathleen H., Campbell, Peter J., and Tubio, Jose M. C.
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- 2023
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13. Parallel RNA and DNA analysis after deep sequencing (PRDD-seq) reveals cell type-specific lineage patterns in human brain
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Huang, August Yue, Li, Pengpeng, Rodin, Rachel E., Kim, Sonia N., Dou, Yanmei, Kenny, Connor J., Akula, Shyam K., Hodge, Rebecca D., Bakken, Trygve E., Miller, Jeremy A., Lein, Ed S., Park, Peter J., Lee, Eunjung Alice, and Walsh, Christopher A.
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- 2020
14. Teacher qualification matters: The association between cumulative teacher qualification and students’ educational attainment
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Lee, Se Woong and Lee, Eunjung Alice
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- 2020
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15. Somatic cancer driver mutations are enriched and associated with inflammatory states in Alzheimer’s disease microglia
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Huang, August Yue, primary, Zhou, Zinan, additional, Talukdar, Maya, additional, Miller, Michael B., additional, Chhouk, Brian, additional, Enyenihi, Liz, additional, Rosen, Ila, additional, Stronge, Edward, additional, Zhao, Boxun, additional, Kim, Dachan, additional, Choi, Jaejoon, additional, Khoshkhoo, Sattar, additional, Kim, Junho, additional, Ganz, Javier, additional, Travaglini, Kyle, additional, Gabitto, Mariano, additional, Hodge, Rebecca, additional, Kaplan, Eitan, additional, Lein, Ed, additional, De Jager, Philip L., additional, Bennett, David A., additional, Lee, Eunjung Alice, additional, and Walsh, Christopher A., additional
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- 2024
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16. A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders
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Lee, Arthur S, primary, Ayers, Lauren J, additional, Kosicki, Michael, additional, Chan, Wai-Man, additional, Fozo, Lydia N, additional, Pratt, Brandon M, additional, Collins, Thomas E, additional, Zhao, Boxun, additional, Rose, Matthew F, additional, Sanchis-Juan, Alba, additional, Fu, Jack M, additional, Wong, Isaac, additional, Zhao, Xuefang, additional, Tenney, Alan P, additional, Lee, Cassia, additional, Laricchia, Kristen M, additional, Barry, Brenda J, additional, Bradford, Victoria R, additional, Lek, Monkol, additional, MacArthur, Daniel G, additional, Lee, Eunjung Alice, additional, Talkowski, Michael E, additional, Brand, Harrison, additional, Pennacchio, Len A, additional, and Engle, Elizabeth C, additional
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- 2023
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17. Comprehensive identification of transposable element insertions using multiple sequencing technologies
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Chu, Chong, Borges-Monroy, Rebeca, Viswanadham, Vinayak V., Lee, Soohyun, Li, Heng, Lee, Eunjung Alice, and Park, Peter J.
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- 2021
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18. Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
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Borges-Monroy, Rebeca, Chu, Chong, Dias, Caroline, Choi, Jaejoon, Lee, Soohyun, Gao, Yue, Shin, Taehwan, Park, Peter J., Walsh, Christopher A., and Lee, Eunjung Alice
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- 2021
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19. Genomic approaches to trace the history of human brain evolution with an emerging opportunity for transposon profiling of ancient humans
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Wang, Yilan, Zhao, Boxun, Choi, Jaejoon, and Lee, Eunjung Alice
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- 2021
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20. APP gene copy number changes reflect exogenous contamination
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Kim, Junho, Zhao, Boxun, Huang, August Yue, Miller, Michael B., Lodato, Michael A., Walsh, Christopher A., and Lee, Eunjung Alice
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Glycoproteins -- Genetic aspects ,Messenger RNA -- Contamination ,Genomes -- Contamination ,Copy number variations -- Analysis ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Author(s): Junho Kim [sup.1] [sup.2] [sup.3] , Boxun Zhao [sup.1] [sup.2] [sup.3] , August Yue Huang [sup.1] [sup.2] [sup.3] , Michael B. Miller [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] [sup.6] , [...]
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- 2020
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21. Novel Alzheimer’s disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers
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Park, Jong-Ho, Park, Inho, Youm, Emilia Moonkyung, Lee, Sejoon, Park, June-Hee, Lee, Jongan, Lee, Dong Young, Byun, Min Soo, Lee, Jun Ho, Yi, Dahyun, Chung, Sun Ju, Park, Kye Won, Choi, Nari, Kim, Seong Yoon, Yoon, Woon, An, Hoyoung, Kim, Ki woong, Choi, Seong Hye, Jeong, Jee Hyang, Kim, Eun-Joo, Kang, Hyojin, Lee, Junehawk, Kim, Younghoon, Lee, Eunjung Alice, Seo, Sang Won, Na, Duk L., and Kim, Jong-Won
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- 2021
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22. Impaired neural stress resistance and loss of REST in bipolar disorder
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Meyer, Katharina, primary, Ling, King-Hwa, additional, Yeo, Pei-Ling, additional, Spathopoulou, Angeliki, additional, Drake, Derek, additional, Choi, Jaejoon, additional, Aron, Liviu, additional, Garcia-Corral, Mariana, additional, Ko, Tak, additional, Lee, Eunjung Alice, additional, Tam, Jenny M., additional, Perlis, Roy H., additional, Church, George M., additional, Tsai, Li-Huei, additional, and Yankner, Bruce A., additional
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- 2023
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23. Contribution and therapeutic implications of retroelement insertions in ataxia telangiectasia
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Zhao, Boxun, primary, Nguyen, Minh A., additional, Woo, Sijae, additional, Kim, Jinkuk, additional, Yu, Timothy W., additional, and Lee, Eunjung Alice, additional
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- 2023
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24. Pan-cancer analysis reveals multifaceted roles of retrotransposon-fusion RNAs
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Lee, Boram, primary, Park, Junseok, additional, Voshall, Adam, additional, Maury, Eduardo, additional, Kang, Yeeok, additional, Kim, Yoen Jeong, additional, Lee, Jin-Young, additional, Shim, Hye-Ran, additional, Kim, Hyo-Ju, additional, Lee, Jung-Woo, additional, Jung, Min-Hyeok, additional, Kim, Si-Cho, additional, Khanh Chu, Hoang Bao, additional, Kim, Da-Won, additional, Kim, Minjeong, additional, Choi, Eun-Ji, additional, Hwang, Ok Kyung, additional, Lee, Ho Won, additional, Ha, Kyungsoo, additional, Choi, Jung Kyoon, additional, Kim, Yongjoon, additional, Choi, Yoonjoo, additional, Park, Woong-Yang, additional, and Lee, Eunjung Alice, additional
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- 2023
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25. Abstract P2063: Cellular Fusion Drives Polyploidization In Human Cardiomyocytes
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Sivankutty, Indu, primary, Jung, Lucy, additional, Huang, August Y, additional, Araten, Sarah, additional, Hilal, Nazia, additional, Walsh, Christopher, additional, Lee, Eunjung Alice, additional, Chen, Ming Hui, additional, and Choudhury, Sangita, additional
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- 2023
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26. Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy
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Khoshkhoo, Sattar, primary, Wang, Yilan, additional, Chahine, Yasmine, additional, Erson-Omay, E. Zeynep, additional, Robert, Stephanie M., additional, Kiziltug, Emre, additional, Damisah, Eyiyemisi C., additional, Nelson-Williams, Carol, additional, Zhu, Guangya, additional, Kong, Wenna, additional, Huang, August Yue, additional, Stronge, Edward, additional, Phillips, H. Westley, additional, Chhouk, Brian H., additional, Bizzotto, Sara, additional, Chen, Ming Hui, additional, Adikari, Thiuni N., additional, Ye, Zimeng, additional, Witkowski, Tom, additional, Lai, Dulcie, additional, Lee, Nadine, additional, Lokan, Julie, additional, Scheffer, Ingrid E., additional, Berkovic, Samuel F., additional, Haider, Shozeb, additional, Hildebrand, Michael S., additional, Yang, Edward, additional, Gunel, Murat, additional, Lifton, Richard P., additional, Richardson, R. Mark, additional, Blümcke, Ingmar, additional, Alexandrescu, Sanda, additional, Huttner, Anita, additional, Heinzen, Erin L., additional, Zhu, Jidong, additional, Poduri, Annapurna, additional, DeLanerolle, Nihal, additional, Spencer, Dennis D., additional, Lee, Eunjung Alice, additional, Walsh, Christopher A., additional, and Kahle, Kristopher T., additional
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- 2023
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27. Characterizing the molecular impact of KMT2D variants on the epigenetic and transcriptional landscapes in kabuki syndrome
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Jung, Youngsook Lucy, primary, Hung, Christina, additional, Choi, Jaejoon, additional, Lee, Eunjung Alice, additional, and Bodamer, Olaf, additional
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- 2023
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28. Data from Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain
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Ganz, Javier, primary, Maury, Eduardo A., primary, Becerra, Basheer, primary, Bizzotto, Sara, primary, Doan, Ryan N., primary, Kenny, Connor J., primary, Shin, Taehwan, primary, Kim, Junho, primary, Zhou, Zinan, primary, Ligon, Keith L., primary, Lee, Eunjung Alice, primary, and Walsh, Christopher A., primary
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- 2023
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29. Table S1 from Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain
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Ganz, Javier, primary, Maury, Eduardo A., primary, Becerra, Basheer, primary, Bizzotto, Sara, primary, Doan, Ryan N., primary, Kenny, Connor J., primary, Shin, Taehwan, primary, Kim, Junho, primary, Zhou, Zinan, primary, Ligon, Keith L., primary, Lee, Eunjung Alice, primary, and Walsh, Christopher A., primary
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- 2023
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30. Supplementary Data from Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain
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Ganz, Javier, primary, Maury, Eduardo A., primary, Becerra, Basheer, primary, Bizzotto, Sara, primary, Doan, Ryan N., primary, Kenny, Connor J., primary, Shin, Taehwan, primary, Kim, Junho, primary, Zhou, Zinan, primary, Ligon, Keith L., primary, Lee, Eunjung Alice, primary, and Walsh, Christopher A., primary
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- 2023
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31. Impaired neural stress resistance and loss of REST in bipolar disorder
- Author
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Meyer, Katharina, Ling, King-Hwa, Yeo, Pei-Ling, Spathopoulou, Angeliki, Drake, Derek, Choi, Jaejoon, Aron, Liviu, Garcia-Corral, Mariana, Ko, Tak, Lee, Eunjung Alice, Tam, Jenny M., Perlis, Roy H., Church, George M., Tsai, Li-Huei, Yankner, Bruce A., Meyer, Katharina, Ling, King-Hwa, Yeo, Pei-Ling, Spathopoulou, Angeliki, Drake, Derek, Choi, Jaejoon, Aron, Liviu, Garcia-Corral, Mariana, Ko, Tak, Lee, Eunjung Alice, Tam, Jenny M., Perlis, Roy H., Church, George M., Tsai, Li-Huei, and Yankner, Bruce A.
- Abstract
Neurodevelopmental changes and impaired stress resistance have been implicated in the pathogenesis of bipolar disorder (BD), but the underlying regulatory mechanisms are unresolved. Here we describe a human cerebral organoid model of BD that exhibits altered neural development, elevated neural network activity, and a major shift in the transcriptome. These phenotypic changes were reproduced in cerebral organoids generated from iPS cell lines derived in different laboratories. The BD cerebral organoid transcriptome showed highly significant enrichment for gene targets of the transcriptional repressor REST. This was associated with reduced nuclear REST and REST binding to target gene recognition sites. Reducing the oxygen concentration in organoid cultures to a physiological range ameliorated the developmental phenotype and restored REST expression. These effects were mimicked by treatment with lithium. Reduced nuclear REST and derepression of REST targets genes were also observed in the prefrontal cortex of BD patients. Thus, an impaired cellular stress response in BD cerebral organoids leads to altered neural development and transcriptional dysregulation associated with downregulation of REST. These findings provide a new model and conceptual framework for exploring the molecular basis of BD.
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- 2023
32. Global impact of somatic structural variation on the DNA methylome of human cancers
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Zhang, Yiqun, Yang, Lixing, Kucherlapati, Melanie, Hadjipanayis, Angela, Pantazi, Angeliki, Bristow, Christopher A., Lee, Eunjung Alice, Mahadeshwar, Harshad S., Tang, Jiabin, Zhang, Jianhua, Seth, Sahil, Lee, Semin, Ren, Xiaojia, Song, Xingzhi, Sun, Huandong, Seidman, Jonathan, Luquette, Lovelace J., Xi, Ruibin, Chin, Lynda, Protopopov, Alexei, Park, Peter J., Kucherlapati, Raju, and Creighton, Chad J.
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- 2019
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33. Somatic Ras/Raf/MAPK Variants Enriched in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy
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Khoshkhoo, Sattar, primary, Wang, Yilan, additional, Chahine, Yasmine, additional, Erson-Omay, E. Zeynep, additional, Robert, Stephanie, additional, Kiziltug, Emre, additional, Damisah, Eyiyemisi C., additional, Nelson-Williams, Carol, additional, Zhu, Guangya, additional, Kong, Wenna, additional, Huang, August Yue, additional, Stronge, Edward, additional, Phillips, H. Westley, additional, Chhouk, Brian H., additional, Bizzotto, Sara, additional, Chen, Ming Hui, additional, Adikari, Thiuni N., additional, Ye, Zimeng, additional, Witkowski, Tom, additional, Lai, Dulcie, additional, Lee, Nadine, additional, Lokan, Julie, additional, Scheffer, Ingrid E., additional, Berkovic, Samuel F., additional, Haider, Shozeb, additional, Hildebrand, Michael S., additional, Yang, Edward, additional, Gunel, Murat, additional, Lifton, Richard P., additional, Richardson, R Mark, additional, Blümcke, Ingmar, additional, Alexandrescu, Sanda, additional, Huttner, Anita, additional, Heinzen, Erin L., additional, Zhu, Jidong, additional, Poduri, Annapurna, additional, DeLanerolle, Nihal, additional, Spencer, Dennis D., additional, Lee, Eunjung Alice, additional, Walsh, Christopher A., additional, and Kahle, Kristopher T., additional
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- 2022
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34. 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, 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Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
- Subjects
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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35. Combined burden and functional impact tests for cancer driver discovery using DriverPower
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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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36. Integrative pathway enrichment analysis of multivariate omics data
- Author
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Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, 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Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. 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 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
- Published
- 2023
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37. Pathway and network analysis of more than 2500 whole cancer genomes
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
- Published
- 2023
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38. Divergent mutational processes distinguish hypoxic and normoxic tumours
- Author
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Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, 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, Al-Shahrour, Fatima, 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, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, 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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. 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 quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
- Published
- 2023
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39. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Sieverling, Lina, Hong, Chen, Koser, Sandra D, Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M, Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J, Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C, Alvarez, Eva G, Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C, Bowtell, David DL, Brors, Benedikt, Burns, Kathleen H, Campbell, Peter J, Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J, Edwards, Paul A, Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W, Gerstein, Mark, Gordenin, Dmitry A, Haan, David, Haber, James E, Hess, Julian M, Imielinski, Marcin, Jones, David TW, Ju, Young Seok, Kazanov, Marat D, Klimczak, Leszek J, Koh, Youngil, Korbel, Jan O, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G, Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio CP, Ossowski, Stephan, Pearson, John V, Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D, Roberts, Steven A, Rodriguez-Martin, Bernardo, Schumacher, Steven E, Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Stewart, Chip, Torrents, David, MC Tubio, Jose, Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A, Weischenfeldt, Joachim, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, 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, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Bailey, Matthew H, Bailey, Peter J, 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, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Biankin, Andrew V, 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, 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, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, 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-Seng-Yue, Michelle, Chandan, Vishal S, Chang, David K, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, 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, Cooke, Susanna L, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, 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, Deshpande, Vikram, 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, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Eyfjord, Jorunn E, Faltas, Bishoy M, Fan, Daiming, Fan, Yu, Faquin, William C, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Field, Matthew A, 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, 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, Garraway, Levi, Garred, Øystein, Garrison, Erik, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstung, Moritz, Getz, Gad, 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, 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, Grimmond, Sean M, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haas, Siegfried, Haase, Kerstin, Habermann, Nina, Hach, Faraz, Haider, Syed, 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, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hoadley, Katherine A, 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, 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, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, 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, Jiao, Wei, 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, Nic, Jones, Steven JM, Jonkers, Jos, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kahles, Andre, Kahraman, Abdullah, Kaiser, Vera B, 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, Kato, Mamoru, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, 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, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Komorowski, Jan, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, 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, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Kübler, Kirsten, 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, Lazar, Alexander J, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Hee Jin, 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, Constance H, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, 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, Louis, David N, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, 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, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin, Sancha, Martin-Subero, Jose I, 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, 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, Miyoshi, Naoki, Mizuno, Shinichi, Molnár-Gábor, Fruzsina, Moore, Malcolm J, Moore, Richard A, Morganella, Sandro, Morris, Quaid D, Morrison, Carl, Mose, Lisle E, Moser, Catherine D, Muiños, Ferran, Mularoni, Loris, Mungall, Andrew J, Mungall, Karen, Musgrove, Elizabeth A, Mustonen, Ville, Mutch, David, Muyas, Francesc, Muzny, Donna M, Muñoz, Alfonso, Myers, Jerome, Myklebost, Ola, Möller, Peter, Nagae, Genta, Nagrial, Adnan M, Nahal-Bose, Hardeep K, Nakagama, Hitoshi, Nakamura, Hiromi, Nakamura, Toru, Nakano, Kaoru, Nandi, Tannistha, Nangalia, Jyoti, Nastic, Mia, Navarro, Arcadi, Neal, David E, Nettekoven, Gerd, Newell, Felicity, Newhouse, Steven J, Newton, Yulia, Ng, Alvin Wei Tian, Ng, Anthony, Nicholson, Jonathan, Nicol, David, Nie, Yongzhan, Nielsen, G Petur, Nielsen, Morten Muhlig, Nik-Zainal, Serena, Noble, Michael S, Nones, Katia, Northcott, Paul A, Notta, Faiyaz, O’Connor, Brian D, O’Donnell, Peter, O’Donovan, Maria, O’Meara, Sarah, O’Neill, Brian Patrick, O’Neill, J Robert, Ocana, David, Ochoa, Angelica, Oesper, Layla, Ogden, Christopher, Ohdan, Hideki, Ohi, Kazuhiro, Ohno-Machado, Lucila, Oien, Karin A, Ojesina, Akinyemi I, Ojima, Hidenori, Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, Prinz, Manuel, Pritchard, Antonia L, Prokopec, Stephenie D, Provenzano, Elena, Puente, Xose S, Puig, Sonia, Pulido-Tamayo, Sergio, Pupo, Gulietta M, Purdie, Colin A, Quinn, Michael C, Rabionet, Raquel, Rader, Janet S, Radlwimmer, Bernhard, Radovic, Petar, Raeder, Benjamin, Raine, Keiran M, Ramakrishna, Manasa, Ramakrishnan, Kamna, Ramalingam, Suresh, Raphael, Benjamin J, Rathmell, W Kimryn, Rausch, Tobias, Reifenberger, Guido, Reimand, Jüri, Reis-Filho, Jorge, Reuter, Victor, Reyes-Salazar, Iker, Reyna, Matthew A, Reynolds, Sheila M, Rheinbay, Esther, Riazalhosseini, Yasser, Richardson, Andrea L, Richter, Julia, Ringel, Matthew, Ringnér, Markus, Rino, Yasushi, Roach, Jeffrey, Roberts, Lewis R, Robertson, A Gordon, Robertson, Alan J, Rodriguez, Javier Bartolomé, Rodríguez-González, F Germán, Roehrl, Michael HA, Rohde, Marius, Rokutan, Hirofumi, Romieu, Gilles, Rooman, Ilse, Roques, Tom, Rosebrock, Daniel, Rosenberg, Mara, Rosenstiel, Philip C, Rosenwald, Andreas, Rowe, Edward W, Royo, Romina, Rozen, Steven G, Rubanova, Yulia, Rubin, Mark A, Rubio-Perez, Carlota, Rudneva, Vasilisa A, Rusev, Borislav C, Ruzzenente, Andrea, Rätsch, Gunnar, Sabarinathan, Radhakrishnan, Sabelnykova, Veronica Y, Sadeghi, Sara, Sahinalp, S Cenk, Saini, Natalie, Saito-Adachi, Mihoko, Saksena, Gordon, Salcedo, Adriana, Salgado, Roberto, Salichos, Leonidas, Sallari, Richard, Saller, Charles, Salvia, Roberto, Sam, Michelle, Samra, Jaswinder S, Sanchez-Vega, Francisco, Sander, Chris, Sanders, Grant, Sarin, Rajiv, Sarrafi, Iman, Sasaki-Oku, Aya, Sauer, Torill, Sauter, Guido, Saw, Robyn PM, Scardoni, Maria, Scarlett, Christopher J, Scarpa, Aldo, Scelo, Ghislaine, Schadendorf, Dirk, Schein, Jacqueline E, Schilhabel, Markus B, Schlomm, Thorsten, Schmidt, Heather K, Schramm, Sarah-Jane, Schreiber, Stefan, Schultz, Nikolaus, Schwarz, Roland F, Scolyer, Richard A, Scott, David, Seethala, Raja, Segre, Ayellet V, Selander, Iris, Semple, Colin A, Senbabaoglu, Yasin, Sengupta, Subhajit, Sereni, Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, Staaf, Johan, Stadler, Peter F, Staib, Peter, Stark, Stefan G, Stebbings, Lucy, Stefánsson, Ólafur Andri, Stegle, Oliver, Stein, Lincoln D, Stenhouse, Alasdair, Stilgenbauer, Stephan, Stobbe, Miranda D, Stratton, Michael R, Stretch, Jonathan R, Struck, Adam J, Stuart, Joshua M, Stunnenberg, Henk G, Su, Hong, Su, Xiaoping, Sun, Ren X, Sungalee, Stephanie, Susak, Hana, Suzuki, Akihiro, Sweep, Fred, Szczepanowski, Monika, Sültmann, Holger, Yugawa, Takashi, Tam, Angela, Tamborero, David, Tan, Benita Kiat Tee, Tan, Donghui, Tan, Patrick, Tanaka, Hiroko, Taniguchi, Hirokazu, Tanskanen, Tomas J, Tarabichi, Maxime, Tarnuzzer, Roy, Tarpey, Patrick, Taschuk, Morgan L, Tatsuno, Kenji, Tavaré, Simon, Taylor, Darrin F, Taylor-Weiner, Amaro, Teague, Jon W, Teh, Bin Tean, Tembe, Varsha, Temes, Javier, Thai, Kevin, Thayer, Sarah P, Thiessen, Nina, Thomas, Gilles, Thomas, Sarah, Thompson, Alan, Thompson, Alastair M, Thompson, John FF, Thompson, R Houston, Thorne, Heather, Thorne, Leigh B, Thorogood, Adrian, Tiao, Grace, Tijanic, Nebojsa, Timms, Lee E, Tirabosco, Roberto, Tojo, Marta, Tommasi, Stefania, Toon, Christopher W, Toprak, Umut H, Tortora, Giampaolo, Tost, Jörg, Totoki, Yasushi, Townend, David, Traficante, Nadia, Treilleux, Isabelle, Trotta, Jean-Rémi, Trümper, Lorenz HP, Tsao, Ming, Tsunoda, Tatsuhiko, Tucker, Olga, Turkington, Richard, Turner, Daniel J, Tutt, Andrew, Ueno, Masaki, Ueno, Naoto T, Umbricht, Christopher, Umer, Husen M, Underwood, Timothy J, Urban, Lara, Urushidate, Tomoko, Ushiku, Tetsuo, Uusküla-Reimand, Liis, Valencia, Alfonso, Van Den Berg, David J, Van Laere, Steven, Van Loo, Peter, Van Meir, Erwin G, Van den Eynden, Gert G, Van der Kwast, Theodorus, Vasudev, Naveen, Vazquez, Miguel, Vedururu, Ravikiran, Veluvolu, Umadevi, Vembu, Shankar, Verbeke, Lieven PC, Vermeulen, Peter, Verrill, Clare, Viari, Alain, Vicente, David, Vicentini, Caterina, VijayRaghavan, K, Viksna, Juris, Vilain, Ricardo E, Vincent-Salomon, Anne, Visakorpi, Tapio, Voet, Douglas, Vyas, Paresh, Vázquez-García, Ignacio, Waddell, Nick M, Wadelius, Claes, Wadi, Lina, Wagener, Rabea, Wang, Jian, Wang, Jiayin, Wang, Linghua, Wang, Qi, Wang, Wenyi, Wang, Yumeng, Wang, Zhining, Waring, Paul M, Warnatz, Hans-Jörg, Warrell, Jonathan, Warren, Anne Y, Waszak, Sebastian M, Wedge, David C, Weichenhan, Dieter, Weinberger, Paul, Weinstein, John N, Weisenberger, Daniel J, Welch, Ian, Wendl, Michael C, Werner, Johannes, Whalley, Justin P, Wheeler, David A, Whitaker, Hayley C, Wigle, Dennis, Wilkerson, Matthew D, Williams, Ashley, Wilmott, James S, Wilson, Gavin W, Wilson, Julie M, Wilson, Richard K, Winterhoff, Boris, Wintersinger, Jeffrey A, Wiznerowicz, Maciej, Wolf, Stephan, Wong, Bernice H, Wong, Tina, Wong, Winghing, Woo, Youngchoon, Wood, Scott, Wouters, Bradly G, Wright, Adam J, Wright, Derek W, Wright, Mark H, Wu, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Zhenggang, Xi, Liu, Xia, Tian, Xiang, Qian, Xiao, Xiao, Xing, Rui, Xiong, Heng, Xu, Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van 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
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
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- 2023
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40. OP024: Discovery and therapeutic implications of pathogenic retroelements in neurodegenerative diseases
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Zhao, Boxun, primary, Larson, Austin, additional, Hu, Chunguang, additional, Chiabrando, Deborah, additional, Chin, Diana, additional, McCourt, Emily, additional, Bertino, Francesca, additional, Kim, Jinkuk, additional, Seferian, Megan, additional, Nguyen, Minh, additional, Woo, Sijae, additional, Suslovitch, Victoria, additional, Lee, Eunjung Alice, additional, and Yu, Timothy, additional
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- 2022
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41. Persistent DNA damage associated with ATM kinase deficiency promotes microglial dysfunction
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Bourseguin, Julie, primary, Cheng, Wen, additional, Talbot, Emily, additional, Hardy, Liana, additional, Lai, Jenny, additional, Jeffries, Ailsa M, additional, Lodato, Michael A, additional, Lee, Eunjung Alice, additional, and Khoronenkova, Svetlana V, additional
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- 2022
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42. Identification of Somatic Mutations From Bulk and Single-Cell Sequencing Data
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Huang, August Yue, primary and Lee, Eunjung Alice, additional
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- 2022
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43. Abstract 9854: Somatic Mutations in Single Human Cardiomyocytes Reveal Rapid Age-Related DNA Damage and Cardiomyocyte Fusion
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Choudhury, Sangita, primary, Huang, August Yue, additional, Kim, Junho, additional, Morillo, Katherine, additional, Maury, Eduardo, additional, Zhou, Zinan, additional, Araten, Sarah, additional, Lee, Eunjung Alice, additional, Walsh, Christopher A, additional, and Chen, Ming H, additional
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- 2021
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44. Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers
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Bim, Larissa Valdemarin, primary, Carneiro, Thaise Nayane Ribeiro, additional, Buzatto, Vanessa Candiotti, additional, Colozza-Gama, Gabriel Avelar, additional, Koyama, Fernanda C., additional, Thomaz, Debora Mota Dias, additional, de Jesus Paniza, Ana Carolina, additional, Lee, Eunjung Alice, additional, Galante, Pedro Alexandre Favoretto, additional, and Cerutti, Janete Maria, additional
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- 2021
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45. Single-nucleus transcriptomic analyses reveal microglial activation underlying cerebellar degeneration in Ataxia Telangiectasia
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Lai, Jenny, primary, Kim, Junho, additional, Jeffries, Ailsa M., additional, Tolles, Allie, additional, Chittenden, Thomas W., additional, Buckley, Patrick G., additional, Yu, Timothy W, additional, Lodato, Michael A., additional, and Lee, Eunjung Alice, additional
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- 2021
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46. Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain
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Ganz, Javier, primary, Maury, Eduardo A., additional, Becerra, Basheer, additional, Bizzotto, Sara, additional, Doan, Ryan N., additional, Kenny, Connor J., additional, Shin, Taehwan, additional, Kim, Junho, additional, Zhou, Zinan, additional, Ligon, Keith L., additional, Lee, Eunjung Alice, additional, and Walsh, Christopher A., additional
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- 2021
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47. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
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Xi, Ruibin, Jain, Dhawal, Jung, Youngsook L., Yang, Lixing, Gordenin, Dmitry, Pellman, David S., Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C., Bowtell, David D. L., Brors, Benedikt, Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Cortés-Ciriano, Isidro, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Miyano, Satoru, Nakagawa, Hidewaki, Navarro, Fabio C. P., Ossowski, Stephan, Park, Peter J., Pearson, John V., Puiggròs, Montserrat, Rippe, Karsten, Roberts, Nicola D., Roberts, Steven A., Rodriguez-Martin, Bernardo, Schumacher, Steven E., Scully, Ralph, Shackleton, Mark, Sidiropoulos, Nikos, Sieverling, Lina, Stewart, Chip, Torrents, David, Tubio, Jose M. C., Villasante, Izar, Waddell, Nicola, Wala, Jeremiah A., Weischenfeldt, Joachim, Yao, Xiaotong, Yoon, Sung-Soo, Zamora, Jorge, Zhang, Cheng-Zhong, Cortés-Ciriano, Isidro [0000-0002-2036-494X], Lee, Jake June-Koo [0000-0003-1348-4094], Xi, Ruibin [0000-0001-7545-7361], Gordenin, Dmitry [0000-0002-8399-1836], Klimczak, Leszek J. [0000-0003-3048-2576], Zhang, Cheng-Zhong [0000-0001-8825-7158], Park, Peter J. [0000-0001-9378-960X], and Apollo - University of Cambridge Repository
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631/67 ,45 ,analysis ,631/208/212 ,45/23 ,631/114 - Abstract
Funder: Ludwig Center at Harvard, Funder: National Cancer Institute: K22CA193848, Funder: US National Institutes of Health Intramural Research Program Project Z1AES103266, Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.
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- 2021
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48. Additional file 1 of Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder
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Borges-Monroy, Rebeca, Chu, Chong, Dias, Caroline, Choi, Jaejoon, Lee, Soohyun, Gao, Yue, Shin, Taehwan, Park, Peter J., Walsh, Christopher A., and Lee, Eunjung Alice
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Additional file 1: Supplementary Methods, Figure S1. The version of xTea used in this study has a high performance and is comparable to MELT in short-read Illumina WGS data. Figure S2. Polymorphic and de novo transposable element insertions (TEIs) in the SSC cohort. Figure S3. The number of Alu TEIs detected per individual is different for some populations. Figure S4. Percentage of insertions which were not found in previous studies (novel) or overlap with TEIs from previous analyses (known). Figure S5. Target site duplication (TSD) size distribution for de novo and polymorphic novel and known non-reference (KNR) TEIs. Figure S6. Comparison of population allele frequencies (PAFs) between unrelated parental individuals in the SSC cohort and gnomAD-SV TEIs. Figure S7. The observed number of de novo TEIs in high probability of being loss of function intolerant (pLI) genes compared to expected TEIs based on 10,000 random simulations. Figure S8. The observed number of de novo TEIs in SFARI ASD genes and high pLI genes compared to expected TEIs based on 10,000 random simulations using a position probability matrix to consider the L1 endonuclease cleavage site. Figure S9. Parental age at birth of children with and without TEIs for cases and controls combined. Figure S10. Estimated insertion size of TEIs. Figure S11. Enrichment and depletion of TEIs in coding and gene regulatory regions. Figure S12. Enrichment and depletion of TEIs in coding and gene regulatory regions. Table S1. Polymorphic insertions sample sizes. Table S3. De novo insertion rates and sample sizes. Table S4. De novo insertions that overlap the top 10% expressed genes in the neocortex during development. Table S5. Number of de novo insertions overlapping regions with epigenetic annotation in fetal brain. Table S6. Number of observed polymorphic insertions in parental SSC samples overlapping regions with epigenetic annotation in fetal brain. Table S8. Memory and time cost of xTea on different numbers of CPU cores.
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- 2021
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49. Evidence of Cooperation between Hippo Pathway and RAS Mutation in Thyroid Carcinomas
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Carneiro, Thaise Nayane Ribeiro, primary, Bim, Larissa Valdemarin, additional, Buzatto, Vanessa Candiotti, additional, Galdeno, Vanessa, additional, Asprino, Paula Fontes, additional, Lee, Eunjung Alice, additional, Galante, Pedro Alexandre Favoretto, additional, and Cerutti, Janete Maria, additional
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- 2021
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50. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
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Akdemir, Kadir C., Le, Victoria T., Chandran, Sahaana, Li, Yilong, Verhaak, Roel G., Beroukhim, Rameen, Campbell, Peter J., Chin, Lynda, Dixon, Jesse R., Futreal, P. Andrew, Alvarez, Eva G., Baez-Ortega, Adrian, Boutros, Paul C., Bowtell, David D.L., Brors, Benedikt, Burns, Kathleen H., Chan, Kin, Chen, Ken, Cortés-Ciriano, Isidro, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Jones, David T.W., Ju, Young Seok, Kazanov, Marat D., Klimczak, Leszek J., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June Koo, Sidiropoulos, Nikos, Weischenfeldt, Joachim, Futreal, P Andrew [0000-0001-8663-2671], Apollo - University of Cambridge Repository, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, and University of St Andrews. Cellular Medicine Division
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QH301 Biology ,Genoma humà ,Genome ,Medical and Health Sciences ,Cromatina ,chemistry.chemical_compound ,0302 clinical medicine ,Neoplasms ,2.1 Biological and endogenous factors ,Aetiology ,Cancer ,Regulation of gene expression ,Gene Rearrangement ,0303 health sciences ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,3rd-DAS ,Biological Sciences ,Chromatin ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,PCAWG Structural Variation Working Group ,Human ,Biotechnology ,Genomic Structural Variation ,QH426 Genetics ,Computational biology ,Biology ,Article ,RC0254 ,QH301 ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Genetics ,Humans ,Data mining ,QH426 ,Gene ,Tumors ,030304 developmental biology ,Neoplastic ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Genome, Human ,Human Genome ,PCAWG Consortium ,Gene rearrangement ,Human genetics ,Reordenament genètic ,chemistry ,Gene Expression Regulation ,Gene expression ,Genètica ,DNA ,Developmental Biology - Abstract
Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold., A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.
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- 2020
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