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Author Correction: Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer

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NPJ breast cancer 2023年第1期9卷 11页

作者： Shivangi Yadav Ranya Virk Carolina H Chung Mariana Bustamante Eduardo David VanDerway Duojiao Chen Kirsten Burdett Hongyu Gao Zexian Zeng Manish Ranjan Gannon Cottone Xiaoling Xuei Sriram Chandrasekaran Vadim Backman Robert Chatterton Seema Ahsan Khan Susan E Clare Department of Surgery Feinberg School of Medicine Northwestern University Chicago IL 60611 USA. Department of Biomedical Engineering Northwestern University Evanston IL 60208-2850 USA. Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USA. Center of for Medical Genomics Indiana University School of Medicine Indianapolis IN 46202 USA. Department of Preventive Medicine Northwestern University Chicago IL 60611 USA. Department of Data Sciences Dana Farber Cancer Institute Harvard T.H. Chan School of Public Health Boston MA 02215 USA. Program in Chemical Biology University of Michigan Ann Arbor MI 48109 USA. Rogel Cancer Center University of Michigan Medical School Ann Arbor MI 48109 USA. Center for Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI 48109 USA. Department of Obstetrics and Gynecology Northwestern University Feinberg School of Medicine Chicago IL 60611 USA. Department of Surgery Feinberg School of Medicine Northwestern University Chicago IL 60611 USA. s-khan2@northwestern.edu. Department of Surgery Feinberg School of Medicine Northwestern University Chicago IL 60611 USA. susan.clare@northwestern.edu.

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Publisher Correction: Comprehensive molecular characterization of mitochondrial genomes in human cancers

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Nature genetics 2023年第5期55卷 893页

作者： Yuan Yuan Young Seok Ju Youngwook Kim Jun Li Yumeng Wang Christopher J Yoon Yang Yang Inigo Martincorena Chad J Creighton John N Weinstein Yanxun Xu Leng Han Hyung-Lae Kim Hidewaki Nakagawa Keunchil Park Peter J Campbell Han Liang Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology Daejeon Korea. Department of Health Science and Technology Samsung Advanced Institute for Health Science and Technology Sungkyunkwan University School of Medicine Seoul Korea. Quantitative and Computational Biosciences Graduate Program Baylor College of Medicine Houston TX USA. Division of Biostatistics The University of Texas Health Science Center at Houston School of Public Health Houston TX USA. Department of Medicine and Dan L. Duncan Cancer Center Division of Biostatistics Baylor College of Medicine Houston TX USA. Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Applied Mathematics and Statistics Johns Hopkins University Baltimore MD USA. Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston McGovern Medical School Houston TX USA. Department of Biochemistry Ewha Womans University School of Medicine Seoul Korea. Laboratory for Cancer Genomics RIKEN Center for Integrative Medical Sciences Yokohama Japan. Division of Hematology/Oncology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea. kpark@skku.edu. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK. pc8@sanger.ac.uk. Cambridge University Hospitals NHS Foundation Trust Cambridge UK. pc8@sanger.ac.uk. Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston TX USA. hliang1@***. Quantitative and Computational Biosciences Graduate Program Baylor College of Medicine Houston TX USA. hliang1@***. Department of Systems Biology The University of Texas MD Anderson Cancer Center Houston TX USA. hliang1@mdanderson

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Author Correction: An atlas of dynamic chromatin landscapes in mouse fetal development

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Nature 2020年第7831期586卷 E31页

作者： David U Gorkin Iros Barozzi Yuan Zhao Yanxiao Zhang Hui Huang Ah Young Lee Bin Li Joshua Chiou Andre Wildberg Bo Ding Bo Zhang Mengchi Wang J Seth Strattan Jean M Davidson Yunjiang Qiu Veena Afzal Jennifer A Akiyama Ingrid Plajzer-Frick Catherine S Novak Momoe Kato Tyler H Garvin Quan T Pham Anne N Harrington Brandon J Mannion Elizabeth A Lee Yoko Fukuda-Yuzawa Yupeng He Sebastian Preissl Sora Chee Jee Yun Han Brian A Williams Diane Trout Henry Amrhein Hongbo Yang J Michael Cherry Wei Wang Kyle Gaulton Joseph R Ecker Yin Shen Diane E Dickel Axel Visel Len A Pennacchio Bing Ren Ludwig Institute for Cancer Research La Jolla CA USA. Center for Epigenomics University of California San Diego School of Medicine La Jolla CA USA. Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA. Department of Surgery and Cancer Imperial College London London UK. Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA USA. Biomedical Sciences Graduate Program University of California San Diego School of Medicine La Jolla CA USA. Department of Pediatrics University of California San Diego School of Medicine La Jolla CA USA. Department of Cellular and Molecular Medicine University of California San Diego School of Medicine La Jolla CA USA. Department of Biochemistry and Molecular Biology Penn State School of Medicine Hershey PA USA. Stanford University School of Medicine Department of Genetics Stanford CA USA. Genomic Analysis Laboratory Salk Institute for Biological Studies La Jolla CA USA. Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA. Howard Hughes Medical Institute Salk Institute for Biological Studies La Jolla CA USA. Institute for Human Genetics and University of California San Francisco San Francisco CA USA. Department of Neurology University of California San Francisco San Francisco CA USA. Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA. avisel@lbl.gov. US Department of Energy Joint Genome Institute Berkeley CA USA. avisel@lbl.gov. School of Natural Sciences University of California Merced Merced CA USA. avisel@lbl.gov. Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA. lapennacchio@lbl.gov. US Department of Energy Joint Genome Institute Berkeley CA USA. lapennacchio@lbl.gov. Comparative Biochemistry Program University of California Berkeley Berkeley CA USA

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Author Correction: Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer

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Nature 2024年第8011期629卷 E9页

作者： Lanbo Xiao Abhijit Parolia Yuanyuan Qiao Pushpinder Bawa Sanjana Eyunni Rahul Mannan Sandra E Carson Yu Chang Xiaoju Wang Yuping Zhang Josh N Vo Steven Kregel Stephanie A Simko Andrew D Delekta Mustapha Jaber Heng Zheng Ingrid J Apel Lisa McMurry Fengyun Su Rui Wang Sylvia Zelenka-Wang Sanjita Sasmal Leena Khare Subhendu Mukherjee Chandrasekhar Abbineni Kiran Aithal Mital S Bhakta Jay Ghurye Xuhong Cao Nora M Navone Alexey I Nesvizhskii Rohit Mehra Ulka Vaishampayan Marco Blanchette Yuzhuo Wang Susanta Samajdar Murali Ramachandra Arul M Chinnaiyan Michigan Center for Translational Pathology University of Michigan Ann Arbor MI USA. Department of Pathology University of Michigan Ann Arbor MI USA. Molecular and Cellular Pathology Program University of Michigan Ann Arbor MI USA. Rogel Cancer Center University of Michigan Ann Arbor MI USA. Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI USA. Aurigene Discovery Technologies Electronic City Phase II Bangalore India. Dovetail Genomics Scotts Valley CA USA. Howard Hughes Medical Institute University of Michigan Ann Arbor MI USA. Department of Genitourinary Medical Oncology and the David H. Koch Center for Applied Research of Genitourinary Cancers The University of Texas MD Anderson Cancer Center Houston TX USA. Department of Internal Medicine/Oncology University of Michigan Ann Arbor MI USA. Vancouver Prostate Centre Vancouver British Columbia Canada. Department of Urologic Sciences University of British Columbia Vancouver British Columbia V6T 1Z3 Canada. Michigan Center for Translational Pathology University of Michigan Ann Arbor MI USA. arul@umich.edu. Department of Pathology University of Michigan Ann Arbor MI USA. arul@umich.edu. Rogel Cancer Center University of Michigan Ann Arbor MI USA. arul@umich.edu. Department of Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI USA. arul@umich.edu. Howard Hughes Medical Institute University of Michigan Ann Arbor MI USA. arul@umich.edu. Department of Urology University of Michigan Ann Arbor MI USA. arul@umich.edu.

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Polygenic risk modeling for prediction of epithelial ovarian cancer risk (vol 30, pg 349, 2021)

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EUROPEAN JOURNAL OF HUMAN GENETICS 2022年第5期30卷 630-631页

作者： Dareng, Eileen O. Tyrer, Jonathan P. Barnes, Daniel R. Jones, Michelle R. Yang, Xin Aben, Katja K. H. Adank, Muriel A. Agata, Simona Andrulis, Irene L. Anton-Culver, Hoda Antonenkova, Natalia N. Aravantinos, Gerasimos Arun, Banu K. Augustinsson, Annelie Balmana, Judith Bandera, Elisa V. Barkardottir, Rosa B. Barrowdale, Daniel Beckmann, Matthias W. Beeghly-Fadiel, Alicia Benitez, Javier Bermisheva, Marina Bernardini, Marcus Q. Bjorge, Line Black, Amanda Bogdanova, Natalia V. Bonanni, Bernardo Borg, Ake Brenton, James D. Budzilowska, Agnieszka Butzow, Ralf Buys, Saundra S. Cai, Hui Caligo, Maria A. Campbell, Ian Cannioto, Rikki Cassingham, Hayley Chang-Claude, Jenny Chanock, Stephen J. Chen, Kexin Chiew, Yoke-Eng Chung, Wendy K. Claes, Kathleen B. M. Colonna, Sarah Cook, Linda S. Couch, Fergus J. Daly, Mary B. Dao, Fanny Davies, Eleanor de la Hoya, Miguel de Putter, Robin Dennis, Joe DePersia, Allison Devilee, Peter Diez, Orland Ding, Yuan Chun Doherty, Jennifer A. Domchek, Susan M. Dork, Thilo du Bois, Andreas Durst, Matthias Eccles, Diana M. Eliassen, Heather A. Engel, Christoph Evans, Gareth D. Fasching, Peter A. Flanagan, James M. Fortner, Renee T. Machackova, Eva Friedman, Eitan Ganz, Patricia A. Garber, Judy Gensini, Francesca Giles, Graham G. Glendon, Gord Godwin, Andrew K. Goodman, Marc T. Greene, Mark H. Gronwald, Jacek Hahnen, Eric Haiman, Christopher A. Hakansson, Niclas Hamann, Ute Hansen, Thomas V. O. Harris, Holly R. Hartman, Mikael Heitz, Florian Hildebrandt, Michelle A. T. Hogdall, Estrid Hogdall, Claus K. Hopper, John L. Huang, Ruea-Yea Huff, Chad Hulick, Peter J. Huntsman, David G. Imyanitov, Evgeny N. Isaacs, Claudine Jakubowska, Anna James, Paul A. Janavicius, Ramunas Jensen, Allan Johannsson, Oskar Th. John, Esther M. Jones, Michael E. Kang, Daehee Karlan, Beth Y. Karnezis, Anthony Kelemen, Linda E. Khusnutdinova, Elza Kiemeney, Lambertus A. Kim, Byoung-Gie Kjaer, Susanne K. Komenaka, Ian Kupryjanczyk, Jolanta Kurian, Allison W. Kwong, Ava Lambrechts, Diether Larson, Melissa C. Lazaro, Conxi L University of Cambridge Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Cambridge UK University of Cambridge Centre for Cancer Genetic Epidemiology Department of Oncology Cambridge UK Center for Bioinformatics and Functional Genomics Cedars-Sinai Medical Center Los Angeles CA USA Radboud University Medical Center Radboud Institute for Health Sciences Nijmegen The Netherlands Netherlands Comprehensive Cancer Organisation Utrecht The Netherlands The Netherlands Cancer Institute—Antoni van Leeuwenhoek hospital Family Cancer Clinic Amsterdam The Netherlands Veneto Institute of Oncology IOV—IRCCS Immunology and Molecular Oncology Unit Padua Italy Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital Fred A. Litwin Center for Cancer Genetics Toronto ON Canada University of Toronto Department of Molecular Genetics Toronto ON Canada University of California Irvine Department of Epidemiology Genetic Epidemiology Research Institute Irvine CA USA N.N. Alexandrov Research Institute of Oncology and Medical Radiology Minsk Belarus ‘Agii Anargiri’ Cancer Hospital Athens Greece University of Texas MD Anderson Cancer Center Department of Breast Medical Oncology Houston TX USA Lund University Department of Cancer Epidemiology Clinical Sciences Lund Sweden Vall d’Hebron Institute of Oncology Hereditary cancer Genetics Group Barcelona Spain University Hospital of Vall d’Hebron Department of Medical Oncology Barcelona Spain Rutgers Cancer Institute of New Jersey Cancer Prevention and Control Program New Brunswick NJ USA Landspitali University Hospital Department of Pathology Reykjavik Iceland University of Iceland BMC (Biomedical Centre) Faculty of Medicine Reykjavik Iceland University Hospital Erlangen Friedrich-Alexander-University Erlangen-Nuremberg Department of Gynecology and Obstetrics Comprehensive Cancer Center ER-EMN Erlangen Germany Vanderbilt University School of Medicine Division of Epidemiology Department

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

关键词： Clinical genetics Genetic markers Risk factors Biomedicine general Human Genetics bioinformatics Gene Expression Cytogenetics

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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

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NATURE GENETICS 2018年第12期50卷 1755-1755页

作者： Evangelou, Evangelos Warren, Helen R. Mosen-Ansorena, David Mifsud, Borbala Pazoki, Raha Gao, He Ntritsos, Georgios Dimou, Niki Cabrera, Claudia P. Karaman, Ibrahim Fu Liang Ng Evangelou, Marina Witkowska, Katarzyna Tzanis, Evan Hellwege, Jacklyn N. Giri, Ayush Edwards, Digna R. Velez Sun, Yan V. Cho, Kelly Gaziano, J. Michael Wilson, Peter W. F. Tsao, Philip S. Kovesdy, Csaba P. Esko, Tonu Magi, Reedik Milani, Lili Almgren, Peter Boutin, Thibaud Debette, Stephanie Ding, Jun Giulianini, Franco Holliday, Elizabeth G. Jackson, Anne U. Li-Gao, Ruifang Lin, Wei-Yu Luan, Jian'an Mangino, Massimo Oldmeadow, Christopher Prins, Bram Peter Qian, Yong Sargurupremraj, Muralidharan Shah, Nabi Surendran, Praveen Theriault, Sebastien Verweij, Niek Willems, Sara M. Zhao, Jing-Hua Amouyel, Philippe Connell, John de Mutsert, Renee Doney, Alex S. F. Farrall, Martin Menni, Cristina Morris, Andrew D. Noordam, Raymond Pare, Guillaume Poulter, Neil R. Shields, Denis C. Stanton, Alice Thom, Simon Abecasis, Goncalo Amin, Najaf Arking, Dan E. Ayers, Kristin L. Barbieri, Caterina M. Batini, Chiara Bis, Joshua C. Blake, Tineka Bochud, Murielle Boehnke, Michael Boerwinkle, Eric Boomsma, Dorret I. Bottinger, Erwin P. Braund, Peter S. Brumat, Marco Campbell, Archie Campbell, Harry Chakravarti, Aravinda Chambers, John C. Chauhan, Ganesh Ciullo, Marina Cocca, Massimiliano Collins, Francis Cordell, Heather J. Davies, Gail de Borst, Martin H. de Geus, Eco J. Deary, Ian J. Deelen, Joris Del Greco, Fabiola M. Demirkale, Cumhur Yusuf Dorr, Marcus Ehret, Georg B. Elosua, Roberto Enroth, Stefan Erzurumluoglu, A. Mesut Ferreira, Teresa Franberg, Mattias Franco, Oscar H. Gandin, Ilaria Gasparini, Paolo Giedraitis, Vilmantas Gieger, Christian Girotto, Giorgia Goel, Anuj Gow, Alan J. Gudnason, Vilmundur Guo, Xiuqing Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Harris, Sarah E. Hartman, Catharina A. Havulinna, Aki S. Hicks, Andrew A. Hofer, Edith Hofman, Albert Hottenga, Jouke-Jan Huffman, Jennifer E. Hwang, Shih-Jen Ingelsson, Erik James, Alan Jansen Department of Epidemiology and Biostatistics Imperial College London London UK Department of Hygiene and Epidemiology University of Ioannina Medical School Ioannina Greece William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK National Institute for Health Research Barts Cardiovascular Biomedical Research Center Queen Mary University of London London UK MRC-PHE Centre for Environment and Health Imperial College London London UK Department of Mathematics Imperial College London London UK Division of Epidemiology Department of Medicine Institute for Medicine and Public Health Vanderbilt Genetics Institute Vanderbilt University Medical Center Tennessee Valley Healthcare System (626)/Vanderbilt University Nashville TN USA Vanderbilt Genetics Institute Vanderbilt Epidemiology Center Department of Obstetrics and Gynecology Vanderbilt University Medical Center Tennessee Valley Health Systems VA Nashville TN USA Department of Epidemiology Emory University Rollins School of Public Health Atlanta GA USA Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) VA Boston Healthcare System Boston MA USA Division of Aging Department of Medicine Brigham and Women’s Hospital Department of Medicine Harvard Medical School Boston MA USA Atlanta VAMC and Emory Clinical Cardiovascular Research Institute Atlanta GA USA VA Palo Alto Health Care System Division of Cardiovascular Medicine Stanford University School of Medicine Stanford CA USA Nephrology Section Memphis VA Medical Center and University of Tennessee Health Science Center Memphis TN USA Estonian Genome Center University of Tartu Tartu Estonia Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA Department Clinical Sciences Malmö Lund University Malmö Sweden MRC Human Genetics Un

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

关键词： Cardiovascular diseases Genome informatics Genome-wide association studies

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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries (vol 55, pg 89, 2023)

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NATURE GENETICS 2023年第3期55卷 519-520页

作者： Fernandez-Rozadilla, Ceres Timofeeva, Maria Chen, Zhishan Law, Philip Thomas, Minta Schmit, Stephanie Diez-Obrero, Virginia Hsu, Li Fernandez-Tajes, Juan Palles, Claire Sherwood, Kitty Briggs, Sarah Svinti, Victoria Donnelly, Kevin Farrington, Susan Blackmur, James Vaughan-Shaw, Peter Shu, Xiao-ou Long, Jirong Cai, Qiuyin Guo, Xingyi Lu, Yingchang Broderick, Peter Studd, James Huyghe, Jeroen Harrison, Tabitha Conti, David Dampier, Christopher Devall, Mathew Schumacher, Fredrick Melas, Marilena Rennert, Gad Obon-Santacana, Mireia Martin-Sanchez, Vicente Moratalla-Navarro, Ferran Oh, Jae Hwan Kim, Jeongseon Jee, Sun Ha Jung, Keum Ji Kweon, Sun-Seog Shin, Min-Ho Shin, Aesun Ahn, Yoon-Ok Kim, Dong-Hyun Oze, Isao Wen, Wanqing Matsuo, Keitaro Matsuda, Koichi Tanikawa, Chizu Ren, Zefang Gao, Yu-Tang Jia, Wei-Hua Hopper, John Jenkins, Mark Win, Aung Ko Pai, Rish Figueiredo, Jane Haile, Robert Gallinger, Steven Woods, Michael Newcomb, Polly Duggan, David Cheadle, Jeremy Kaplan, Richard Maughan, Timothy Kerr, Rachel Kerr, David Kirac, Iva Bohm, Jan Mecklin, Lukka-Pekka Jousilahti, Pekka Knekt, Paul Aaltonen, Lauri Rissanen, Harri Pukkala, Eero Eriksson, Johan Cajuso, Tatiana Hanninen, Ulrika Kondelin, Johanna Palin, Kimmo Tanskanen, Tomas Renkonen-Sinisalo, Laura Zanke, Brent Mannisto, Satu Albanes, Demetrius Weinstein, Stephanie Ruiz-Narvaez, Edward Palmer, Julie Buchanan, Daniel Platz, Elizabeth Visvanathan, Kala Ulrich, Cornelia Siegel, Erin Brezina, Stefanie Gsur, Andrea Campbell, Peter Chang-Claude, Jenny Hoffmeister, Michael Brenner, Hermann Slattery, Martha Potter, John Tsilidis, Konstantinos Schulze, Matthias Gunter, Marc Murphy, Neil Castells, Antoni Castellvi-Bel, Sergi Moreira, Leticia Arndt, Volker Shcherbina, Anna Stern, Mariana Pardamean, Bens Bishop, Timothy Giles, Graham Southey, Melissa Idos, Gregory McDonnell, Kevin Abu-Ful, Zomoroda Greenson, Joel Shulman, Katerina Lejbkowicz, Flavio Offit, Kenneth Su, Yu-Ru Steinfelder, Robert Keku, Temitope van Guelpen, Bethany Hudson, Thomas Hampel, Heather Pearlman, Edinburgh Cancer Research Centre Institute of Genomics and Cancer University of Edinburgh Edinburgh UK Genomic Medicine Group Instituto de Investigacion Sanitaria de Santiago Santiago de Compostela Spain Colon Cancer Genetics Group Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh UK Danish Institute for Advanced Study Department of Public Health University of Southern Denmark Odense Denmark Division of Epidemiology Department of Medicine Vanderbilt-Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University Medical Center Nashville TN USA Division of Genetics and Epidemiology Institute of Cancer Research London UK Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA Genomic Medicine Institute Cleveland Clinic Cleveland OH USA Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland OH USA Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute Barcelona Spain Oncology Data Analytics Program Catalan Institute of Oncology Barcelona Spain Consortium for Biomedical Research in Epidemiology and Public Health Madrid Madrid Spain Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain Department of Biostatistics School of Public Health University of Washington Seattle WA USA Institute of Cancer and Genomic Sciences College of Medical and Dental Sciences University of Birmingham Birmingham UK Department of Public Health Richard Doll Building University of Oxford Oxford UK Department of Biomedical Informatics Vanderbilt University School of Medicine Nashville TN USA Department of Preventive Medicine USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles CA USA Center for Public Health Genomics Department of Public Health Sciences University of Virginia Charlottesville VA USA Department of Populat

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

关键词： Colorectal cancer Epigenomics Genome-wide association studies Transcriptomics

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Whole exome sequencing identifies clinically relevant mutational signatures in resected hepatocellular carcinoma

Liver Cancer International

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Liver Cancer International 2020年第1期1卷

作者： Jason Y. Chan Abner H. Lim Arnoud Boot Elizabeth Lee Cedric C.-Y. Ng Jing Y. Lee Vikneswari Rajasegaran Wei Liu Shane Goh Jing H. Hong Xiaoying Xu Lavina D. Bharwani Chung Y. Chan Alexander Y. F. Chung Peng C. Cheow Chee-Kiat Tan Choon K. Ho Kui H. Liau Winston W. L. Woon Jee K. Low Akhil Chopra Gilberto Lopes Steven G. Rozen Bin T. Teh Alex Y.-C. Chang Division of Medical Oncology National Cancer Centre Singapore Singapore SingHealth Duke-NUS Blood Cancer Centre Singapore Oncology Academic Clinical Program Duke-NUS Medical School Singapore Cancer Science Institute of Singapore National University of Singapore Singapore Dr Jason Y. Chan Division of Medical Oncology National Cancer Centre Singapore 11 Hospital Dr Singapore 169610. Professor Steven G. Rozen Centre for Computational Biology Duke-NUS Medical School Singapore 8 College Rd Singapore 169857. Professor Alex Y. Chang Department of Medical Oncology Tan Tock Seng Hospital Singapore and Department of Oncology Johns Hopkins University 11 Jalan Tan Tock Seng Singapore 308433. Integrated Genomics Platform National Cancer Centre Singapore Singapore Laboratory of Cancer Epigenome National Cancer Centre Singapore Singapore Centre for Computational Biology Duke-NUS Medical School Singapore Program in Cancer and Stem Cell Biology Duke-NUS Medical School Singapore Institute of Molecular and Cell Biology Singapore Department of Medical Oncology Tan Tock Seng Hospital Singapore Department of Hepatopancreatobiliary and Transplant Surgery Singapore General Hospital Singapore Department of Gastroenterology and Hepatology Singapore General Hospital Singapore Department of General Surgery Tan Tock Seng Hospital Singapore LIAU KH Specialist Clinic Mt Elizabeth Novena Hospital Singapore Sylvester Comprehensive Cancer Center University of Miami Coral Gables FL USA Integrated Biostatistics and Bioinformatics Programme Duke-NUS Medical School Singapore Johns Hopkins Singapore Singapore Johns Hopkins University Baltimore MD USA

Background & Aims Most patients develop recurrent disease despite curative surgery for hepatocellular carcinoma (HCC). No standard adjuvant therapy is available and molecular predictors of outcome are poorly understood. Methods We conducted a multicentre pilot study on patients with localized HCC following surgical resection. Patients received up to 6 months of oral gefitinib as adjuvant therapy. Clinical end points included recurrence-free survival (RFS) and overall survival (OS), and exploratory analyses were conducted from whole exome sequencing data. Results A total of 65 patients were screened for the study, of which 40 were eligible. The median age was 63 years (range, 44-80). Most patients (80%) were positive for hepatitis B or C. With a median follow-up of 4.5 years, the median RFS was 24 months. Median OS was not reached. High Child-Pugh score and advanced T-stage (3-4) were independent predictors for both OS and RFS. Mutational signatures for exposure to aristolochic acid (AA), as characterized by a majority of T:A > A:T mutations, were observed in 18 cases (55%). HCC without AA mutagenesis was associated with early recurrences or death within 2 years of surgery ( P = .037). HCC with high T > A mutations was associated with better OS (HR 0.29, 95% CI 0.09-0.90, P = .033). Conversely, HCC with high C > T mutations was associated with worse OS (HR 4.55, 95% CI 1.20-17.31, P = .026). Conclusions Mutational signatures may carry prognostic significance in HCC following curative resection. Patient outcomes with gefitinib as adjuvant therapy after resection for HCC were modest, highlighting the need for urgent research in this area of unmet clinical need. *** number, NCT00282100.

关键词： adjuvant therapy aristolochic acid mutational signatures prognostic biomarker tyrosine kinase inhibitor

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Correction: Robustness of cancer microbiome signals over a broad range of methodological variation

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Oncogene 2024年第20期43卷 1579页

作者： Gregory D Sepich-Poore Daniel McDonald Evguenia Kopylova Caitlin Guccione Qiyun Zhu George Austin Carolina Carpenter Serena Fraraccio Stephen Wandro Tomasz Kosciolek Stefan Janssen Jessica L Metcalf Se Jin Song Jad Kanbar Sandrine Miller-Montgomery Robert Heaton Rana Mckay Sandip Pravin Patel Austin D Swafford Tal Korem Rob Knight Department of Bioengineering University of California San Diego La Jolla CA USA. Micronoma San Diego CA USA. Feinberg School of Medicine Northwestern University Chicago IL USA. Department of Pediatrics University of California San Diego La Jolla CA USA. Clarity Genomics Antwerp Belgium. School of Life Sciences Arizona State University Tempe AZ USA. Department of Biomedical Informatics Columbia University Irving Medical Center New York NY USA. Program for Mathematical Genomics Department of Systems Biology Columbia University Irving Medical Center New York NY USA. Center for Microbiome Innovation University of California San Diego La Jolla CA USA. Malopolska Centre of Biotechnology Jagiellonian University in Kraków Kraków Poland. Algorithmic Bioinformatics Department of Biology and Chemistry Justus Liebig University Gießen Gießen Germany. Department of Animal Sciences Colorado State University Fort Collins CO USA. Department of Medicine University of California San Diego La Jolla CA USA. Department of Psychiatry University of California San Diego La Jolla CA USA. Moores Cancer Center University of California San Diego Health La Jolla CA USA. Department of Obstetrics and Gynecology Columbia University Irving Medical Center New York NY USA. Department of Bioengineering University of California San Diego La Jolla CA USA. rknight@ucsd.edu. Department of Pediatrics University of California San Diego La Jolla CA USA. rknight@ucsd.edu. Center for Microbiome Innovation University of California San Diego La Jolla CA USA. rknight@ucsd.edu. Department of Computer Science and Engineering University of California San Diego La Jolla CA USA. rknight@ucsd.edu.

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Author Correction: Profiling immunoglobulin repertoires across multiple human tissues using RNA sequencing

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Nature communications 2020年第1期11卷 4499页

作者： Igor Mandric Jeremy Rotman Harry Taegyun Yang Nicolas Strauli Dennis J Montoya William Van Der Wey Jiem R Ronas Benjamin Statz Douglas Yao Velislava Petrova Alex Zelikovsky Roberto Spreafico Sagiv Shifman Noah Zaitlen Maura Rossetti K Mark Ansel Eleazar Eskin Serghei Mangul Department of Computer Science University of California Los Angeles 404 Westwood Plaza Los Angeles CA 90095 USA. Department of Clinical Pharmacy School of Pharmacy University of Southern California 1540 Alcazar Street Los Angeles CA 90033 USA. Bioinformatics Interdepartmental Ph.D. Program University of California Los Angeles 611 Charles E. Young Drive East Los Angeles CA 90095-1570 USA. Biomedical Sciences Graduate Program University of California San Francisco 1675 Owens Street Suite 310 San Francisco CA 94143-0523 USA. Department of Molecular Cell and Developmental Biology University of California Los Angeles 610 Charles E. Young Drive South Los Angeles CA 90095 USA. Department of Microbiology Immunology and Molecular Genetics University of California Los Angeles 609 Charles E. Young Drive East Los Angeles CA 90095 USA. Program in Bioinformatics and Integrative Genomics Harvard Medical School 10 Shattuck Street Suite 514 Boston MA 02115 USA. Wellcome Trust Sanger Institute Wellcome Genome Campus Hinxton Cambridge CB10 1SA UK. Department of Computer Science Georgia State University 33 Gilmer Street SE Atlanta GA 30303 USA. The Laboratory of Bioinformatics I.M. Sechenov First Moscow State Medical University Moscow 119991 Russia. Institute for Quantitative and Computational Biosciences University of California Los Angeles 611 Charles E. Young Drive East Los Angeles CA 90095 USA. Department of Genetics The Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem 9190401 Israel. Department of Medicine University of California San Francisco 533 Parnassus Avenue San Francisco CA 94143 USA. Immunogenetics Center Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California Los Angeles 1000 Veteran Avenue Los Angeles CA 90095-1652 USA. Sandler Asthma Basic Research Center Department of Microbiology and Immunology University of California San Francisco 513 Parnass

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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