Author: "Denis, Bertrand" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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22 results on '"Denis, Bertrand"'

1. P392: Rapid complement mediated TMA diagnosis and early intervention in a renal intensive care unit using Nanopore technology

Author: Nadhi Yousfi, Cyril Mousseaux, Marie Mile, Abderaouf Hamza, Cedric Rafat, Yosu Luque, Carine El sissy, Sacha Beaumeunier, Denis Bertrand, Michael Blum, Julien Doudement, Nicolas Philippe, Veronique Fremeaux-Bacchi, and Laurent Mesnard
Subjects: Genetics, QH426-470, Medicine
Published: 2024
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2. Duration of Carbapenemase-Producing Enterobacteriaceae Carriage in Hospital Patients

Author: Yin Mo, Anastasia Hernandez-Koutoucheva, Patrick Musicha, Denis Bertrand, David Lye, Oon Tek Ng, Shannon N. Fenlon, Swaine L. Chen, Moi Lin Ling, Wen Ying Tang, Timothy Barkham, Niranjan Nagarajan, Ben S. Cooper, and Kalisvar Marimuthu
Subjects: Carbapenemase-producing Enterobacteriaceae, antimicrobial resistance, infection prevention and control, carriage, bacteria, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: To determine the duration of carbapenemase-producing Enterobacteriaceae (CPE) carriage, we studied 21 CPE carriers for »1 year. Mean carriage duration was 86 days; probability of decolonization in 1 year was 98.5%, suggesting that CPE-carriers’ status can be reviewed yearly. Prolonged carriage was associated with use of antimicrobial drugs.
Published: 2020
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3. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

Author: Kern Rei Chng, Sock Hoai Chan, Amanda Hui Qi Ng, Chenhao Li, Apinya Jusakul, Denis Bertrand, Andreas Wilm, Su Pin Choo, Damien Meng Yew Tan, Kiat Hon Lim, Roy Soetinko, Choon Kiat Ong, Dan G. Duda, Simona Dima, Irinel Popescu, Chaisiri Wongkham, Zhu Feng, Khay Guan Yeoh, Bin Tean Teh, Puangrat Yongvanit, Sopit Wongkham, Vajaraphongsa Bhudhisawasdi, Narong Khuntikeo, Patrick Tan, Chawalit Pairojkul, Joanne Ngeow, and Niranjan Nagarajan
Subjects: Microbiome, Cancer, Cholangiocarcinoma, Liver fluke, Medicine, Medicine (General), R5-920
Abstract: Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer.
Published: 2016
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4. Household transmission of carbapenemase-producing Enterobacteriaceae: a prospective cohort study

Author: Swaine L. Chen, Shannon N. Fenlon, Oon Tek Ng, Eli N. Perencevich, Timothy Barkham, Kalisvar Marimuthu, David C. Lye, Yin Mo, Ben S. Cooper, Moi Lin Ling, Denis Bertrand, Brenda Ang, Niranjan Nagarajan, and Anastasia Hernandez-Koutoucheva
Subjects: 0301 basic medicine, Microbiology (medical), Carbapenemase-Producing Enterobacteriaceae, Household contact, Transmission rate, 030106 microbiology, Carbapenem-resistant enterobacteriaceae, beta-Lactamases, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, law, Humans, Medicine, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pharmacology, business.industry, Hazard ratio, Enterobacteriaceae Infections, Carbapenem-Resistant Enterobacteriaceae, Infectious Diseases, Transmission (mechanics), business, Cohort study, Demography
Abstract: Objectives To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers. Methods We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE. Results Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (n = 4), blaKPC-2 (n = 3), blaIMP (n = 2), and blaNDM-1 (n = 1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%–26%). Conclusions We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.
Published: 2021

5. Genome Alert!: a standardized procedure for genomic variant reinterpretation and automated genotype-phenotype reassessment in clinical routine

Author: Sophie Coutant, Armelle Luscan, Quentin Fort, Nicolas Soirat, Abdoulaye Hama Diallo, Mélanie Broutin, Julien Thevenon, Nicolas Philippe, Stéphanie Baert-Desurmont, David Geneviève, Raphaël Lanos, Sacha Beaumeunier, Laurent Mesnard, Jean-Marc Costa, Jérôme Audoux, Kevin Yauy, Laure Raymond, Vanna Geromel, Denis Bertrand, Jean-Marc Holder, Stenzel Cackowski, Aïcha Boughalem, Detlef Trost, Anne-Laure Bougé, Gaël Nicolas, Pascale Richard, Nicolas Duforet-Frebourg, François Lecoquierre, and Quentin Testard
Subjects: Population genomics, Reinterpretation, business.industry, Medicine, Clinical significance, Computational biology, Clinical routine, business, Genome, New diagnosis, Exome sequencing, Genotype phenotype
Abstract: Numerous countries have set up population genomics plans, allowing an unprecedented growth in the ability of interpreting variants in human diseases. Retrospective interpretation of sequenced data in the light of the current literature is a major concern of the field. Moreover, such reinterpretation is manual and both the human resources and the variable operating procedures are main bottlenecks.This work describes the Genome Alert! standardized procedure. This open-source method automatically reports changes with potential clinical significance in variant classification between releases of the ClinVar database. Using ClinVar submissions across time, this method assigns gene-disease associations validity category. Genome Alert! was assessed on a retrospective 29 months multicentric series of 5,959 consecutive individuals screened by targeted or exome sequencing.Between July 2017 and December 2019, the retrospective analysis of ClinVar submissions revealed a monthly median of 1,247 changes in variant classification with potential clinical significance and 23 new gene-disease associations. Reexamination of 4,929 targeted sequencing files highlighted 45 changes, which 89% classifications were expert validated, leading to four additional diagnoses. Genome Alert! gene-disease association catalog provided 75 high-confidence associations not available in the OMIM morbid list, where 20% became OMIM morbid 8 months later. Over 356 negative exome sequencing data that were reannotated for variants in these 75 genes, this elective approach led to a new diagnosis.Genome Alert! (https://genomealert.univ-grenoble-alpes.fr/) enables the systematic and reproducible reinterpretation of acquired sequencing data in a clinical routine with a limited human resource impact.Graphical abstract
Published: 2021

6. ConsensusDriver Improves upon Individual Algorithms for Predicting Driver Alterations in Different Cancer Types and Individual Patients

Author: Iain Beehuat Tan, Jia Yu Koh, Denis Bertrand, Chayaporn Suphavilai, Niranjan Nagarajan, Chenhao Li, Sibyl Drissler, and Burton Kuan Hui Chia
Subjects: 0301 basic medicine, Cancer Research, Computer science, Concordance, Computational Biology, Cancer, Functional impact, Computational biology, Gold standard (test), Precision medicine, medicine.disease, Correlation, 03 medical and health sciences, 030104 developmental biology, Genes, Oncology, Neoplasms, Prediction methods, Mutation, medicine, Humans, In patient, Precision Medicine, Transcriptome, Algorithms
Abstract: Existing cancer driver prediction methods are based on very different assumptions and each of them can detect only a particular subset of driver genes. Here we perform a comprehensive assessment of 18 driver prediction methods on more than 3,400 tumor samples from 15 cancer types, all to determine their suitability in guiding precision medicine efforts. We categorized these methods into five groups: functional impact on proteins in general (FI) or specific to cancer (FIC), cohort-based analysis for recurrent mutations (CBA), mutations with expression correlation (MEC), and methods that use gene interaction network-based analysis (INA). The performance of driver prediction methods varied considerably, with concordance with a gold standard varying from 9% to 68%. FI methods showed relatively poor performance (concordance Significance: These findings assess state-of-the-art cancer driver prediction methods and develop a new and improved consensus-based approach for use in precision oncology. Cancer Res; 78(1); 290–301. ©2017 AACR.
Published: 2018

7. Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time

Author: Patrick Tan, Giridharan Periyasamy, Matan Thangavelu Thangavelu, Judice L. Y. Koh, Hiang Khoon Tan, Shen Yon Toh, Daniel Shao-Weng Tan, Joo-Leng Low, Yan Su, Ankur Sharma, Thakshayeni Skanthakumar, Jacqueline S.G. Hwang, Alexander Lezhava, Iain Beehuat Tan, Hannes Hentze, Hui-Sun Leong, Shumei Chia, N. Gopalakrishna Iyer, Xue-Lin Kwang, Kok-Hing Lim, Xiaoqian Zhang, Ramanuj DasGupta, Siang Hui Choo, Fui-Teen Chong, and Denis Bertrand
Subjects: 0301 basic medicine, Oncology, Cell, General Physics and Astronomy, Metastasis, Mice, Inbred NOD, Tumor Cells, Cultured, Neoplasm, Precision Medicine, lcsh:Science, Multidisciplinary, Gefitinib, Gene Expression Regulation, Neoplastic, Phenotype, Treatment Outcome, medicine.anatomical_structure, Head and Neck Neoplasms, Carcinoma, Squamous Cell, Biomarker (medicine), Mouth Neoplasms, medicine.drug, medicine.medical_specialty, Science, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Carcinoma, Animals, Humans, Adaptor Proteins, Signal Transducing, business.industry, Cancer, YAP-Signaling Proteins, General Chemistry, Phosphoproteins, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Drug Resistance, Neoplasm, Quinazolines, lcsh:Q, Cisplatin, business, Ex vivo, Transcription Factors
Abstract: Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we present a “phenotype-driven precision-oncology” approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of “screenable” patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models. Importantly, PDCs could guide clinical practice and predict tumour progression in two n = 1 co-clinical trials. Comprehensive “-omics” interrogation of PDCs derived from one of these models revealed YAP1 as a putative biomarker for treatment response and survival in ~24% of oral squamous cell carcinoma. We envision that scaling of the proposed PDC approach could uncover biomarkers for therapeutic stratification and guide real-time therapeutic decisions in the future., Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs.
Published: 2017

8. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

Author: Apinya Jusakul, Sopit Wongkham, Chaisiri Wongkham, Patrick Tan, Irinel Popescu, Sock Hoai Chan, Amanda Hui Qi Ng, Damien Meng Yew Tan, Denis Bertrand, Su Pin Choo, Narong Khuntikeo, Khay Guan Yeoh, Chawalit Pairojkul, Chenhao Li, Bin Tean Teh, Dan G. Duda, Kern Rei Chng, Puangrat Yongvanit, Choon Kiat Ong, Roy Soetinko, Andreas Wilm, Simona Dima, Joanne Ngeow, Kiat Hon Lim, Niranjan Nagarajan, Zhu Feng, and Vajaraphongsa Bhudhisawasdi
Subjects: 0301 basic medicine, Male, Pathology, lcsh:Medicine, Bile Duct Neoplasm, Opisthorchiasis, Cholangiocarcinoma, 0302 clinical medicine, RNA, Ribosomal, 16S, Opisthorchis, Opisthorchis viverrini, Cancer, lcsh:R5-920, Bile duct, Microbiota, Gastrointestinal Microbiome, General Medicine, Biodiversity, Middle Aged, 3. Good health, Bifidobacteriaceae, medicine.anatomical_structure, Cell Transformation, Neoplastic, Organ Specificity, 030220 oncology & carcinogenesis, Female, lcsh:Medicine (General), Research Paper, Adult, medicine.medical_specialty, Biology, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, Medicine, General & Internal, parasitic diseases, medicine, Animals, Humans, Microbiome, Aged, fungi, lcsh:R, Liver fluke, medicine.disease, biology.organism_classification, 030104 developmental biology, Bile Duct Neoplasms, Commentary, Metagenome, Metagenomics
Abstract: Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer., Highlights • Stenotrophomonas, implicated in bile duct infections, is enriched in tumor tissues of non-fluke related cholangiocarcinoma. • O. viverrini infection may alter composition of bile duct tissue microbiomes. • Enteric bacteria with metabolic outputs linked to carcinogenesis are enriched in O. viverrini associated tissue microbiomes. The link between microbiota and cancer of the gastrointestinal (GI) tract has been extensively studied. However, the role of tissue microbiome in cholangiocarcinoma (CCA), cancer of the bile duct (an organ connected to the GI tract), is largely unknown. In this study, we detected intriguing compositional differences in the tissue microbiomes of liver fluke related and non-related CCA. Taken together, our data suggests a connection between parasitic infections, tissue microbiome alterations, tissue micro-environment changes and CCA development.
Published: 2016
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9. Comprehensive Characterization of Cancer Driver Genes and Mutations

Author: Matthew H. Bailey, Collin Tokheim, Eduard Porta-Pardo, Sohini Sengupta, Denis Bertrand, Amila Weerasinghe, Antonio Colaprico, Michael C. Wendl, Jaegil Kim, Brendan Reardon, Patrick Kwok-Shing Ng, Kang Jin Jeong, Song Cao, Zixing Wang, Jianjiong Gao, Qingsong Gao, Fang Wang, Eric Minwei Liu, Loris Mularoni, Carlota Rubio-Perez, Niranjan Nagarajan, Isidro Cortés-Ciriano, Daniel Cui Zhou, Wen-Wei Liang, Julian M. Hess, Venkata D. Yellapantula, David Tamborero, Abel Gonzalez-Perez, Chayaporn Suphavilai, Jia Yu Ko, Ekta Khurana, Peter J. Park, Eliezer M. Van Allen, Han Liang, Michael S. Lawrence, Adam Godzik, Nuria Lopez-Bigas, Josh Stuart, David Wheeler, Gad Getz, Ken Chen, Alexander J. Lazar, Gordon B. Mills, Rachel Karchin, Li Ding, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, David I. Heiman, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Katherine A. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. 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Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoadley K.A., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., 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B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Godzik A., Lopez-Bigas N., Stuart J., Wheeler D., Chen K., and Karchin R.
Subjects: 0301 basic medicine, Oncology, Entropy, Programmed Cell Death 1 Receptor, biochemistry, genetics, molecular Biology (all), Biochemistry, B7-H1 Antigen, structure analysi, Principal Component Analysi, Neoplasms, Databases, Genetic, LS2_1, LS4_6, Missense mutation, Statistical analysis, 610 Medicine & health, Exome sequencing, Confusion, Principal Component Analysis, Melanoma, Sciences bio-médicales et agricoles, structure analysis, Algorithm, oncology, Cancer gene, Adenocarcinoma, Microsatellite Instability, ALGORITMOS, medicine.symptom, Algorithms, Human, medicine.medical_specialty, driver gene discovery, Computational biology, Biology, Characterization (mathematics), General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, Internal medicine, medicine, Humans, mutations of clinical relevance, Gene, Biochemistry, Genetics and Molecular Biology(all), Microsatellite instability, Computational Biology, Cancer, medicine.disease, Cancérologie, 030104 developmental biology, Precision oncology, Mutation, Neoplasm, Human genome, Colon adenocarcinoma, human activities, Genetics and Molecular Biology(all)
Abstract: Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence- and structure-based analyses identified >3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%–85% of predicted mutations as likely drivers. We found that >300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors. A comprehensive analysis of oncogenic driver genes and mutations in >9,000 tumors across 33 cancer types highlights the prevalence of clinically actionable cancer driver events in TCGA tumor samples., 0, info:eu-repo/semantics/published
Published: 2018

10. Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

Author: Li Ding, Matthew H. Bailey, Eduard Porta-Pardo, Vesteinn Thorsson, Antonio Colaprico, Denis Bertrand, David L. Gibbs, Amila Weerasinghe, Kuan-lin Huang, Collin Tokheim, Isidro Cortés-Ciriano, Reyka Jayasinghe, Feng Chen, Lihua Yu, Sam Sun, Catharina Olsen, Jaegil Kim, Alison M. Taylor, Andrew D. Cherniack, Rehan Akbani, Chayaporn Suphavilai, Niranjan Nagarajan, Joshua M. Stuart, Gordon B. Mills, Matthew A. Wyczalkowski, Benjamin G. Vincent, Carolyn M. Hutter, Jean Claude Zenklusen, Katherine A. Hoadley, Michael C. Wendl, llya Shmulevich, Alexander J. Lazar, David A. Wheeler, Gad Getz, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, David I. Heiman, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Wei Zhang, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, John N. Weinstein, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, Jose Sebastião Dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Tirapelli, James Catto, Kathy Agnew, Elizabeth Swisher, Jenette Creaney, Bruce Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol Bradford, Thomas Carey, Andrea Haddad, Jeffey Moyer, Lisa Peterson, Mark Prince, Laura Rozek, Gregory Wolf, Rayleen Bowman, Kwun M. Fong, Ian Yang, Robert Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John DiPersio, Bettina Drake, Ramaswamy Govindan, Sharon Heath, Timothy Ley, Brian Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze, Ding L., Bailey M.H., Porta-Pardo E., Thorsson V., Colaprico A., Bertrand D., Gibbs D.L., Weerasinghe A., Huang K.-L., Tokheim C., Cortes-Ciriano I., Jayasinghe R., Chen F., Yu L., Sun S., Olsen C., Kim J., Taylor A.M., Cherniack A.D., Akbani R., Suphavilai C., Nagarajan N., Stuart J.M., Mills G.B., Wyczalkowski M.A., Vincent B.G., Hutter C.M., Zenklusen J.C., Hoadley K.A., Wendl M.C., Shmulevich L., Lazar A.J., Wheeler D.A., Getz G., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Heiman D.I., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Zhang W., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Ng K.-S., Rao A., Ryan M., Wang J., Weinstein J.N., Zhang J., Abeshouse A., Armenia J., Chakravarty D., Chatila W.K., de Bruijn I., Gao J., Gross B.E., Heins Z.J., Kundra R., La K., Ladanyi M., Luna A., Nissan M.G., Ochoa A., Phillips S.M., Reznik E., Sanchez-Vega F., Sander C., Schultz N., Sheridan R., Sumer S.O., Sun Y., Taylor B.S., Anur P., Peto M., Spellman P., Benz C., Wong C.K., Yau C., Hayes D.N., Parker J.S., Wilkerson M.D., Ally A., Balasundaram M., Bowlby R., Brooks D., Carlsen R., Chuah E., Dhalla N., Holt R., Jones S.J.M., Kasaian K., Lee D., Ma Y., Marra M.A., Mayo M., Moore R.A., Mungall A.J., Mungall K., Robertson A.G., Sadeghi S., Schein J.E., Sipahimalani P., Tam A., Thiessen N., Tse K., Wong T., Berger A.C., Beroukhim R., Cibulskis C., Gabriel S.B., Gao G.F., Ha G., Meyerson M., Schumacher S.E., Shih J., Kucherlapati M.H., Kucherlapati R.S., Baylin S., Cope L., Danilova L., Bootwalla M.S., Lai P.H., Maglinte D.T., Van Den Berg D.J., Weisenberger D.J., Auman J.T., Balu S., Bodenheimer T., Fan C., Hoyle A.P., Jefferys S.R., Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., Roman-Roman S., Sastre X., Stern M.-H., Cheng F., Signoretti S., Berchuck A., Bigner D., Lipp E., Marks J., McCall S., McLendon R., Secord A., Sharp A., Behera M., Brat D.J., Chen A., Delman K., Force S., Khuri F., Magliocca K., Maithel S., Olson J.J., Owonikoko T., Pickens A., Ramalingam S., Shin D.M., Sica G., Van Meir E.G., Eijckenboom W., Gillis A., Korpershoek E., Looijenga L., Oosterhuis W., Stoop H., van Kessel K.E., Zwarthoff E.C., Calatozzolo C., Cuppini L., Cuzzubbo S., DiMeco F., Finocchiaro G., Mattei L., Perin A., Pollo B., Chen C., Houck J., Lohavanichbutr P., Hartmann A., Stoehr C., Stoehr R., Taubert H., Wach S., Wullich B., Kycler W., Murawa D., Wiznerowicz M., Chung K., Edenfield W.J., Martin J., Baudin E., Bubley G., Bueno R., De Rienzo A., Richards W.G., Kalkanis S., Mikkelsen T., Noushmehr H., Scarpace L., Girard N., Aymerich M., Campo E., Gine E., Guillermo A.L., Van Bang N., Hanh P.T., Phu B.D., Tang Y., Colman H., Evason K., Dottino P.R., Martignetti J.A., Gabra H., Juhl H., Akeredolu T., Stepa S., Hoon D., Ahn K., Kang K.J., Beuschlein F., Breggia A., Birrer M., Bell D., Borad M., Bryce A.H., Castle E., Chandan V., Cheville J., Copland J.A., Farnell M., Flotte T., Giama N., Ho T., Kendrick M., Kocher J.-P., Kopp K., Moser C., Nagorney D., O'Brien D., O'Neill B.P., Patel T., Petersen G., Que F., Rivera M., Roberts L., Smallridge R., Smyrk T., Stanton M., Thompson R.H., Torbenson M., Yang J.D., Zhang L., Brimo F., Ajani J.A., Gonzalez A.M.A., Behrens C., Bondaruk J., Broaddus R., Czerniak B., Esmaeli B., Fujimoto J., Gershenwald J., Guo C., Logothetis C., Meric-Bernstam F., Moran C., Ramondetta L., Rice D., Sood A., Tamboli P., Thompson T., Troncoso P., Tsao A., Wistuba I., Carter C., Haydu L., Hersey P., Jakrot V., Kakavand H., Kefford R., Lee K., Long G., Mann G., Quinn M., Saw R., Scolyer R., Shannon K., Spillane A., Stretch J., Synott M., Thompson J., Wilmott J., Al-Ahmadie H., Chan T.A., Ghossein R., Gopalan A., Levine D.A., Reuter V., Singer S., Singh B., Tien N.V., Broudy T., Mirsaidi C., Nair P., Drwiega P., Miller J., Smith J., Zaren H., Park J.-W., Hung N.P., Kebebew E., Linehan W.M., Metwalli A.R., Pacak K., Pinto P.A., Schiffman M., Schmidt L.S., Vocke C.D., Wentzensen N., Worrell R., Yang H., Moncrieff M., Goparaju C., Melamed J., Pass H., Botnariuc N., Caraman I., Cernat M., Chemencedji I., Clipca A., Doruc S., Gorincioi G., Mura S., Pirtac M., Stancul I., Tcaciuc D., Albert M., Alexopoulou I., Arnaout A., Bartlett J., Engel J., Gilbert S., Parfitt J., Sekhon H., Thomas G., Rassl D.M., Rintoul R.C., Bifulco C., Tamakawa R., Urba W., Hayward N., Timmers H., Antenucci A., Facciolo F., Grazi G., Marino M., Merola R., de Krijger R., Gimenez-Roqueplo A.-P., Piche A., Chevalier S., McKercher G., Birsoy K., Barnett G., Brewer C., Farver C., Naska T., Pennell N.A., Raymond D., Schilero C., Smolenski K., Williams F., Morrison C., Borgia J.A., Liptay M.J., Pool M., Seder C.W., Junker K., Omberg L., Dinkin M., Manikhas G., Alvaro D., Bragazzi M.C., Cardinale V., Carpino G., Gaudio E., Chesla D., Cottingham S., Dubina M., Moiseenko F., Dhanasekaran R., Becker K.-F., Janssen K.-P., Slotta-Huspenina J., Abdel-Rahman M.H., Aziz D., Bell S., Cebulla C.M., Davis A., Duell R., Elder J.B., Hilty J., Kumar B., Lang J., Lehman N.L., Mandt R., Nguyen P., Pilarski R., Rai K., Schoenfield L., Senecal K., Wakely P., Hansen P., Lechan R., Powers J., Tischler A., Grizzle W.E., Sexton K.C., Kastl A., Henderson J., Porten S., Waldmann J., Fassnacht M., Asa S.L., Schadendorf D., Couce M., Graefen M., Huland H., Sauter G., Schlomm T., Simon R., Tennstedt P., Olabode O., Nelson M., Bathe O., Carroll P.R., Chan J.M., Disaia P., Glenn P., Kelley R.K., Landen C.N., Phillips J., Prados M., Simko J., Smith-McCune K., VandenBerg S., Roggin K., Fehrenbach A., Kendler A., Sifri S., Steele R., Jimeno A., Carey F., Forgie I., Mannelli M., Carney M., Hernandez B., Campos B., Herold-Mende C., Jungk C., Unterberg A., von Deimling A., Bossler A., Galbraith J., Jacobus L., Knudson M., Knutson T., Ma D., Milhem M., Sigmund R., Godwin A.K., Madan R., Rosenthal H.G., Adebamowo C., Adebamowo S.N., Boussioutas A., Beer D., Giordano T., Mes-Masson A.-M., Saad F., Bocklage T., Landrum L., Mannel R., Moore K., Moxley K., Postier R., Walker J., Zuna R., Feldman M., Valdivieso F., Dhir R., Luketich J., Pinero E.M.M., Quintero-Aguilo M., Carlotti C.G., Dos Santos J.S., Kemp R., Sankarankuty A., Tirapelli D., Catto J., Agnew K., Swisher E., Creaney J., Robinson B., Shelley C.S., Godwin E.M., Kendall S., Shipman C., Bradford C., Carey T., Haddad A., Moyer J., Peterson L., Prince M., Rozek L., Wolf G., Bowman R., Fong K.M., Yang I., Korst R., Rathmell W.K., Fantacone-Campbell J.L., Hooke J.A., Kovatich A.J., Shriver C.D., DiPersio J., Drake B., Govindan R., Heath S., Ley T., Van Tine B., Westervelt P., Rubin M.A., Lee J.I., Aredes N.D., Mariamidze A., Clinical sciences, Medical Genetics, Medical Sociology, SAIC-F-Frederick, Inc, and Leidos Biomedical Research, Inc.
Subjects: 0301 basic medicine, oncogenic process, INFORMATION, DNA Repair, Tumor Microenvironment/genetics, Carcinogenesis, Cancer Genome Atlas Research Network, medicine.disease_cause, Genome, Biochemistry, Germline, Transcriptome, oncogenic proce, Neoplasms, Databases, Genetic, LS2_1, Tumor Microenvironment, LS4_6, SOMATIC POINT MUTATIONS, 610 Medicine & health, 11 Medical and Health Sciences, Carcinogenesi, Metabolic Networks and Pathways/genetics, cancer genomic, CARCINOGÊNESE, Genomics, TUMORS, Neoplasms/genetics, omics, Proteome, Physique des particules élémentaires, Microsatellite Instability, Life Sciences & Biomedicine, Metabolic Networks and Pathways, Human, EXPRESSION, Biochemistry & Molecular Biology, cancer, cancer genomics, TCGA, omic, Computational biology, Biology, BREAST, CLASSIFICATION, General Biochemistry, Genetics and Molecular Biology, Article, NO, 03 medical and health sciences, DNA Repair/genetics, medicine, Humans, Tumor microenvironment, Science & Technology, LANDSCAPE, IDENTIFICATION, Biochemistry, Genetics and Molecular Biology(all), Metabolic Networks and Pathway, Cell Biology, Epigenome, 06 Biological Sciences, 030104 developmental biology, DISCOVERY, Mutation, DRIVER, Neoplasm, Carcinogenesis/genetics, Developmental Biology, Genetics and Molecular Biology(all), Genes, Neoplasm
Abstract: The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing. A synthesized view on oncogenic processes based on PanCancer Atlas analyses highlights the complex impact of genome alterations on the signaling and multi-omic profiles of human cancers as well as their influence on tumor microenvironment., 0, info:eu-repo/semantics/published
Published: 2018

11. The pulmonary microbiome in non-cystic fibrosis bronchiectasis

Author: Tuang Yeow Poh, Carrie Kah-Lai Leong, Gan Liang Tan, Teck Boon Low, Sanjay H. Chotirmall, Jia Yu Koh, Albert Yick Hou Lim, Mariko Koh, Anthony Chau Yii, John Abisheganaden, Micheál Mac Aogáin, Amanda Hui Qi Ng, Denis Bertrand, Niranjan Nagarajan, and Ravishankar Chandrasekaran
Subjects: Bronchiectasis, biology, Streptococcus, business.industry, Non cystic fibrosis bronchiectasis, Bacteriome, medicine.disease_cause, medicine.disease, biology.organism_classification, Immunology, Cohort, Haemophilus, medicine, Sputum, Microbiome, medicine.symptom, business
Abstract: Introduction: Pulmonary microbiome composition can predict future exacerbations in bronchiectasis (Rogers G.B., et al. Ann Am Thorac Soc. 2014). To date, most data in this field is derived from Caucasian populations and focuses primarily on the bacterial component of the microbiome (the bacteriome). Consequently little data is available in Asian cohorts, and the fungal component of the microbiome (the mycobiome) is infrequently reported (Chotirmall S., et al. Respirology. 2017). Methods: We prospectively recruited n=59 patients with stable bronchiectasis at three separate clinical sites across Singapore. To determine the bacteriome and mycobiome in patient sputum, we performed shotgun sequencing of 16S rRNA and 18S ITS amplicons respectively. We investigated the correlation between observed microbiome architecture and clinical disease markers in our cohort. Results: Microbiome analysis of our Asian cohort revealed a distinct microbiome in bronchiectasis. The Asian bacteriome was dominated by taxa belonging to Streptococcus , Haemophilus and Pseudomonas species. The bronchiectatic mycobiome was characterised by the predominance of Candida spp. Aspergillus fumigatus and Saccharomyces cerevisiae . Conclusion: Our findings represent the first characterisation of the Asian pulmonary microbiome in bronchiectasis, including analysis of the bacterial and fungal microbiota. The direct and mechanistic implications of these findings on clinical disease, in comparison to Caucasian cohorts, require further investigation. Funding: This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C).
Published: 2017

12. Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Author: Degang Wu, Jinzhuang Dou, Xiaoran Chai, Claire Bellis, Andreas Wilm, Chih Chuan Shih, Wendy Wei Jia Soon, Nicolas Bertin, Clarabelle Bitong Lin, Chiea Chuen Khor, Michael DeGiorgio, Shanshan Cheng, Li Bao, Neerja Karnani, William Ying Khee Hwang, Sonia Davila, Patrick Tan, Asim Shabbir, Angela Moh, Eng-King Tan, Jia Nee Foo, Liuh Ling Goh, Khai Pang Leong, Roger S.Y. Foo, Carolyn Su Ping Lam, Arthur Mark Richards, Ching-Yu Cheng, Tin Aung, Tien Yin Wong, Huck Hui Ng, Jianjun Liu, Chaolong Wang, Matthew Andrew Ackers-Johnson, Edita Aliwarga, Kenneth Hon Kim Ban, Denis Bertrand, John C. Chambers, Dana Leng Hui Chan, Cheryl Xue Li Chan, Miao Li Chee, Miao Ling Chee, Pauline Chen, Yunxin Chen, Elaine Guo Yan Chew, Wen Jie Chew, Lynn Hui Yun Chiam, Jenny Pek Ching Chong, Ivan Chua, Stuart A. Cook, Wei Dai, Rajkumar Dorajoo, Chuan-Sheng Foo, Rick Siow Mong Goh, Axel M. Hillmer, Ishak D. Irwan, Fazlur Jaufeerally, Asif Javed, Justin Jeyakani, John Tat Hung Koh, Jia Yu Koh, Pavitra Krishnaswamy, Jyn Ling Kuan, Neelam Kumari, Ai Shan Lee, Seow Eng Lee, Sheldon Lee, Yen Ling Lee, See Ting Leong, Zheng Li, Peter Yiqing Li, Jun Xian Liew, Oi Wah Liew, Su Chi Lim, Weng Khong Lim, Chia Wei Lim, Tingsen Benson Lim, Choon Kiat Lim, Seet Yoong Loh, Au Wing Lok, Calvin W.L. Chin, Shivani Majithia, Sebastian Maurer-Stroh, Wee Yang Meah, Shi Qi Mok, Niranjan Nargarajan, Pauline Ng, Sarah B. Ng, Zhenyuan Ng, Jessica Yan Xia Ng, Ebonne Ng, Shi Ling Ng, Simon Nusinovici, Chin Thing Ong, Bangfen Pan, Vincent Pedergnana, Stanley Poh, Shyam Prabhakar, Kumar M. Prakash, Ivy Quek, Charumathi Sabanayagam, Wei Qiang See, Yee Yen Sia, Xueling Sim, Wey Cheng Sim, Jimmy So, Dinna K.N. Soon, E. Shyong Tai, Nicholas Y. Tan, Louis C.S. Tan, Hong Chang Tan, Wilson Lek Wen Tan, Moses Tandiono, Amanda Tay, Sahil Thakur, Yih Chung Tham, Zenia Tiang, Grace Li-Xian Toh, Pi Kuang Tsai, Lavanya Veeravalli, Chandra S. Verma, Ling Wang, Min Rui Wang, Wing-Cheong Wong, Zhicheng Xie, Khung Keong Yeo, Liang Zhang, Weiwei Zhai, Yi Zhao, Cardiovascular Centre (CVC), Lee Kong Chian School of Medicine (LKCMedicine), and School of Biological Sciences
Subjects: Male, medicine.medical_specialty, Demographic history, Population, Genome-wide association study, HAPLOTYPE, Biology, VARIANTS, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, ANCESTRY ESTIMATION, 03 medical and health sciences, 0302 clinical medicine, Whole-genome Sequencing, Asian People, HISTORY, medicine, Humans, WIDE ASSOCIATION, Medicine [Science], Selection, Genetic, education, ADAPTATION, 030304 developmental biology, Whole genome sequencing, Singapore, 0303 health sciences, Genetic diversity, education.field_of_study, Whole Genome Sequencing, Asian Populations, Genome, Human, Malaysia, Human genetics, GENOTYPE, MODEL, Genetics, Population, Evolutionary biology, Medical genetics, Female, HEALTH, HUMAN-EVOLUTION, 030217 neurology & neurosurgery, Imputation (genetics)
Abstract: Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version We acknowledge H.M. Kang, S. Das, A. Tan, F. Zhang, J. Terhorst, P.-R. Loh, and G. Hellenthal for helpful discussions and support from all participants and clinical research coordinators of the contributing cohorts and studies: the TTSH Healthy Control Workgroup, the SEED cohort, the Asian Sudden Cardiac Death in Heart Failure Study, the Singapore Heart Failure Outcomes and Phenotypes (SHOP) cohort, the Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT), the Parkinson’s Disease Study, the Peranakan Genome Study, the Platinum Asian Genomes Project, the Bariatric Surgery Study, the National Heart Centre Singapore Biobank and SingHEART cohorts, and the GUSTO and S-PRESTO study groups. This study was supported by Singapore’s A*STAR (core funding and IAF-PP H17/01/a0/007), BMRC (SPF2014/001, SPF2013/002, SPF2014/003, SPF2014/004, and SPF2014/005), NMRC (CIRG/1371/2013, CIRG/1417/2015, CIRG/1488/ 2018, CSA-SI/0012/2017, CG/017/2013, CG/M006/2017_NHCS, TCR/013- NNI/2014, STaR/0011/2012, STaR2013/001, STaR/014/2013, STaR/0026/ 2015, TCR/006-NUHS/2013, TCR/012-NUHS/2014, TCR/004-NUS/2008, TCR/012-NUHS/2014, and center grants 2010-13 and 2013-2017), NRF (NRFF2016-03), National University of Singapore, SingHealth and DukeNUS, and Alexandra Health small innovative grant SIGII/15203 and funding from Huazhong University of Science and Technology, the Tanoto Foundation, the Lee Foundation, the Boston Scientific Investigator Sponsored Research Program and Bayer, the NSF (DEB-1753489), and the Alfred P. Sloan Foundation. The computation was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).
Published: 2019

13. Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion

Author: Jianjun Liu, Lane Wilson, Khek Yu Ho, Marcin Duleba, Niranjan Nagarajan, Florian Kern, Denis Bertrand, Frank McKeon, Yuanyu Hu, Yusuke Yamamoto, Ming Teh, Brooke E. Howitt, Wa Xian, Ting Zhang, Christopher P. Crum, Matthew Vincent, Xia Wang, Hagen Blaszyk, Chiea Chuen Khor, Supriya Srivastava, and Daniil Rolshud
Subjects: 0301 basic medicine, Male, Science, Cellular differentiation, General Physics and Astronomy, medicine.disease_cause, digestive system, General Biochemistry, Genetics and Molecular Biology, Receptor tyrosine kinase, Article, 03 medical and health sciences, Barrett Esophagus, Mice, medicine, Tumor Cells, Cultured, Animals, Humans, Cells, Cultured, Mutation, Multidisciplinary, biology, Stem Cells, Intestinal metaplasia, Cell Differentiation, General Chemistry, Anatomy, medicine.disease, digestive system diseases, surgical procedures, operative, 030104 developmental biology, Dysplasia, biology.protein, Cancer research, Adenocarcinoma, Stem cell, Carcinogenesis, Precancerous Conditions
Abstract: The precancerous lesion known as Barrett's oesophagus can evolve to oesophageal adenocarcinoma in decades-long processes of regenerative growth. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett's, gastric and oesophageal epithelia that yield divergent tumour types following in vitro transformation and xenografting. Genomic analyses reveal a broad mutational spectrum unique to Barrett's stem cells that likely reflects their risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett's initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma though tumour-associated gene amplifications were absent. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett's and define a discrete stem cell underlying its regenerative growth whose eradication could prevent oesophageal adenocarcinoma., Barrett's oesophagus is a precancerous intestinal metaplasia that can progress to oesophageal adenocarcinoma. In this study, the authors isolate and characterize human Barrett's stem cells and identify a specific genomic pedigree that supports the potential role of these cells as precursors of oesophageal adenocarcinoma.
Published: 2015

14. Cloning and variation of ground state intestinal stem cells

Author: Xia Wang, Brooke E. Howitt, Francisco A. Sylvester, Ting Zhang, Niranjan Nagarajan, Khek Yu Ho, Lingyan Wu, Melissa A. Farrow, Lane Wilson, Jeffrey S. Hyams, Roderick T. Bronson, Frank McKeon, Florian Kern, Wa Xian, Denis Bertrand, Benoit Chevalier, Chiea Chuen Khor, D. Borden Lacy, Yue Hong, Yusuke Yamamoto, Thomas J. Devers, Gang Ning, and Christopher P. Crum
Subjects: Colon, Cellular differentiation, Bacterial Toxins, Biology, Regenerative medicine, Epithelium, Genomic Instability, Epigenesis, Genetic, Fetus, Intestine, Small, medicine, Humans, Cell Lineage, Epigenetics, Cells, Cultured, Enterocolitis, Pseudomembranous, Cloning, Gastrointestinal tract, Multidisciplinary, Clostridioides difficile, Stem Cells, Cell Differentiation, Pseudomembranous colitis, Anatomy, Research Highlight, Clone Cells, Cell biology, Intestines, Organoids, medicine.anatomical_structure, Stem cell
Abstract: Stem cells of the gastrointestinal tract, pancreas, liver and other columnar epithelia collectively resist cloning in their elemental states. Here we demonstrate the cloning and propagation of highly clonogenic, 'ground state' stem cells of the human intestine and colon. We show that derived stem-cell pedigrees sustain limited copy number and sequence variation despite extensive serial passaging and display exquisitely precise, cell-autonomous commitment to epithelial differentiation consistent with their origins along the intestinal tract. This developmentally patterned and epigenetically maintained commitment of stem cells is likely to enforce the functional specificity of the adult intestinal tract. Using clonally derived colonic epithelia, we show that toxins A or B of the enteric pathogen Clostridium difficile recapitulate the salient features of pseudomembranous colitis. The stability of the epigenetic commitment programs of these stem cells, coupled with their unlimited replicative expansion and maintained clonogenicity, suggests certain advantages for their use in disease modelling and regenerative medicine.
Published: 2015
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15. The Opisthorchis viverrini genome provides insights into life in the bile duct

Author: Sopit Wongkham, Suling Joyce Lin, Ross S. Hall, Chaisiri Wongkham, Robin B. Gasser, Patrick Tan, Xinhua Yang, Neil D. Young, Andreas Hofmann, Min Hu, Pasi K. Korhonen, Paul W. Sternberg, Wanchai Maleewong, Jun Wang, Helena Safavi-Hemami, Zuo Wang, Denis Bertrand, Niranjan Nagarajan, Bin Tean Teh, Pewpan M. Intapan, Song Gao, Aaron R. Jex, Worasak Kaewkong, and Qihui Seet
Subjects: Molecular Sequence Data, General Physics and Astronomy, Helminth genetics, Opisthorchiasis, General Biochemistry, Genetics and Molecular Biology, Article, Host-Parasite Interactions, Cholangiocarcinoma, Opisthorchis, parasitic diseases, medicine, Animals, Humans, Opisthorchis viverrini, Amino Acid Sequence, Multidisciplinary, Clonorchis sinensis, Genome, biology, Bile duct, Hepatobiliary disease, fungi, General Chemistry, Helminth Proteins, Liver fluke, DNA, Helminth, medicine.disease, biology.organism_classification, medicine.anatomical_structure, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Immunology
Abstract: Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions., The Asian liver fluke is a parasitic worm that is linked to an increased risk of malignant cancer. Here, the authors sequence the draft genome and transcriptome of this fluke and provide insight into how the species has adapted to be able to survive in the bile duct.
Published: 2014

16. Abstract 3414: Genomic signatures of melanoma maintenance

Author: Dave S.B. Hoon, Edison T. Liu, Faranak Ghazi Sherbaf, Axel M. Hillmer, Koichiro Inaki, Xing Y. Woo, and Denis Bertrand
Subjects: Cancer Research, Functional validation, Melanoma, medicine.medical_treatment, Cell, Cancer, Biology, medicine.disease, Bioinformatics, Phenotype, Targeted therapy, Transcriptome, medicine.anatomical_structure, Oncology, medicine, Cancer research, Gene
Abstract: Melanoma is the malignant tumor of melanocytes and considered as one of the most aggressive human cancers. While the worldwide incidence rate of melanoma has increased during the last decade, current therapies for melanoma do not provide long-term effect. The highly heterogeneous expression signature of melanoma underlies the inefficient therapy and accentuates the inevitability of profound molecular understanding of melanoma, its maintenance and progression. In this study, we aimed to reveal the complex patterns of distinct molecular mechanisms underlying the progression and maintenance of melanoma using high-throughput sequencing technologies. Series of melanoma tumor tissues representing discrete stages of the malignant progression were deeply sequenced. Integrative analysis revealed hard-wired genomic aberrations and associated transcriptomic consequences. These genomic aberrations included clusters of oncogenes brought together by structural variations, which cooperated in their amplifications and subsequent up-regulated expressions. We believe that these hard-wired genetic changes are biologically significant; they sustain the survival of the tumor and offer the advantage of the distant metastasis. We reconstituted the architecture of melanoma progression and maintenance and we identified gene cassettes with a putative role in sustaining tumor growth. The correlation of these gene cassettes with the cancer phenotype and the feasibility of these putative oncogenes as candidates for targeted therapy were addressed using cell-based assays on a high content screening platform. Analysis of the matched cell lines derived from the same patient offered a valuable resource for in vitro manipulation, testing of drugs and functional validation. A detailed molecular characterization of the functionally validated genes and their contribution in the cancer signaling pathways will provide a better understanding of the molecular basis of tumor evolution. Citation Format: Faranak Ghazi Sherbaf, Koichiro Inaki, Denis Bertrand, Xing Yi Woo, Dave Hoon, Axel Hillmer, Edison Liu. Genomic signatures of melanoma maintenance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3414. doi:10.1158/1538-7445.AM2014-3414
Published: 2014

17. Abstract 3180: In vitro tool for discovering oncogenes and tumor suppressor genes in a system's manner

Author: Edison T. Liu, Gaye Saginc, Koichiro Inaki, Xing Yi Woo, Charlie Wah Heng Lee, Francesca Menghi, Denis Bertrand, and Leena Ukil
Subjects: Genetics, Cancer Research, Cellular differentiation, Cancer, Suicide gene, Biology, medicine.disease, medicine.disease_cause, Cell biology, Oncology, Cancer stem cell, Cancer cell, medicine, Stem cell, Induced pluripotent stem cell, Carcinogenesis
Abstract: The molecular complexity of cancer still remains as the limiting factor for developing efficient therapies with minimal side effects. However, scientists succeeded in determining common alterations in most human cancer types. Each of these alterations results from disruption of an anti-cancer regulation mechanism and/or activation of cancer-promoting networks by genetic and epigenetic changes. As a consequence, cancer cells become capable of mimicking stem cells’ ability to proliferate indefinitely while maintaining their cellular identity, or to self-renew, which is crucial for any type of stem cell. Indeed, some of the networks which are deregulated in cancer normally regulate self-renewal in stem cells. However, self-renewal is tightly regulated in stem cells, while cancer cells manage to escape the internal and external regulation mechanisms. Hence, cancer cells differ from stem cells by displaying disruptions in feedback mechanism controlling the rate of cell division, aberrant differentiation programs and error-prone replication, so they become invasive and even metastatic. We hypothesize that the stemness regulatory “cassette” that serves limitless replicative potential and undifferentiated state is a measure of cancer virulence and progression. We believe that this gene cassette is established through different mechanisms in each cell type, so it can be separated from invasion and instability in a precise and defined manner. To test our hypotheses, we set up a system reconstruction model consisting of induced pluripotent cells and transformed cells as stem and cancer cell models respectively, and their source of primary mouse embryonic fibroblast cells. From this model system, we created a system's map for transformation using differential expression patterns from whole genome expression arrays. We discovered gene networks that are common between stem and cancer cells, but different from their primary cells of origin. We also found deregulated/activated cassettes which are unique for cancer cells and which are hardwired by genomic rearrangements (copy number and structural variations) identified by DNA paired end tag (DNA-PET) sequencing and single nucleotide variations using RNA sequencing. We are now investigating the role of candidate genes selected from this analysis in cancer and stem cell maintenance through a high content siRNA screening. Citation Format: Gaye Saginc, Leena Ukil, Xingyi Woo, Francesca Menghi, Denis Bertrand, Charlie Wah Heng Lee, Koichiro Inaki, Edison Tak Bun Liu. In vitro tool for discovering oncogenes and tumor suppressor genes in a system's manner. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3180. doi:10.1158/1538-7445.AM2013-3180
Published: 2013

18. Abstract 2001: Genomic signatures of melanoma progression and maintenance

Author: Kelly Chong Chong, Charlie Lee Wah Heng, Donald L. Morton, Xing Yi Woo, Edison T. Liu, Denis Bertrand, Faranak Ghazi Sherbaf, Dave S.B. Hoon, Koichiro Inaki, and Sharon K. Huang
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Candidate gene, business.industry, Melanoma, Clone (cell biology), Cancer, medicine.disease, medicine.anatomical_structure, Internal medicine, Immunology, Cancer cell, medicine, Vemurafenib, business, Lymph node, V600E, medicine.drug
Abstract: Melanoma is one of the most aggressive human cancers. The worldwide incidence rate of melanoma has increased during the last decade but with few FDA approved therapeutic options. Patients with lymph node metastasis can show highly variable clinical outcomes, from several years disease free survival after excision of the primary lesion to extremely aggressive metastatic disease; while patients with distant metastasis show poor clinical outcome. Outstanding outcomes using target therapies such as B-RAF V600E inhibitor (Vemurafenib) bring hope for possibility of melanoma cure. Alternatively, since melanoma acquires resistance to Vemurafenib, the necessity of searching for other candidates and simultaneously targeting several pathways for long-term survival is inevitable. Better understanding of the genomic signatures of melanoma progression and maintenance provides new opportunities for developing novel therapeutic targets for successful management of this fatal disease. In this study, we aim to reveal the complex patterns of distinct molecular aberrations and mechanisms underlying the progression and maintenance of melanoma using high-throughput sequencing approaches. Our hypothesis is that there are genetic changes in melanoma which suggest the survival of the distant metastasis; these genetic changes include activated oncogenes and suppressed tumor suppressor genes correlated with melanoma progression and maintenance. As a proof of principal we initiated this study with a poor prognosis melanoma patient; a 46 year old man diagnosed with lymph node metastasis and treated with T-cell vaccination (TCV), who showed the tumor distant metastasis to lung, 14.8 months after complete lymph node dissection. The availability of primary cell lines established from both lymph node and lung metastatic tissues represents a major advantage for the functional validation of individual candidate genes which may serve as novel targets for cancer therapy. Integration of copy number with structural variation data showed a great selection for cell lines generation (derived from lymph node and lung tumors) and we observed that this selection was for a similar clone embedded in lymph node and lung metastatic tumors. With this data, we hypothesized that common sets of events which cut across all samples in this case identify the core sets of putative oncogenes and tumor suppressor genes which drive this patient's cancer cells. The correlation of these genes with the cancer phenotype will be addressed. Citation Format: Faranak Ghazi Sherbaf, Charlie LEE Wah Heng, Xing Yi Woo, Denis Bertrand, Koichiro Inaki, Kelly Chong Chong, Donald Morton, Sharon Huang, Dave Hoon, Edison Liu. Genomic signatures of melanoma progression and maintenance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2001. doi:10.1158/1538-7445.AM2013-2001
Published: 2013

19. 585 Genomics of Metastatic Progression in Cutaneous Melanoma

Author: C.W. Lee, Edison T. Liu, Xing Yi Woo, F. Ghazi Sherbaf, Denis Bertrand, Donald L. Morton, K. Chong, Koichiro Inaki, Dave S.B. Hoon, and Sharon K. Huang
Subjects: Cancer Research, Oncology, business.industry, Cutaneous melanoma, Cancer research, Medicine, Genomics, business
Published: 2012

20. 606 Defining the Molecular States of Cancer and Stem Cells Through Integrative Transcriptional and Genomic Analysis

Author: Xing Yi Woo, Gaye Saginc, P.E. Jacques, Leena Ukil, A. Hilmer, Denis Bertrand, En-Chih Liu, and C.W.H. Lee
Subjects: Cancer Research, Oncology, medicine, Cancer research, Cancer, Stem cell, Biology, medicine.disease
Published: 2012

21. Abstract 5107: Unravelling the complexity of individual cancer genomes

Author: Roshan Agarwal, Xing Yi Woo, Hani Gabra, Wah Heng Lee, Min Gong, Euan A. Stronach, Wendy Wang, Nona Rama, Krishna Karuturi, Francesca Menghi, Denis Bertrand, Sigrid L. Rouam, and Edison T. Liu
Subjects: Genome instability, Cancer Research, Cancer, Biology, medicine.disease, Bioinformatics, medicine.disease_cause, Genome, Oncology, Ovarian carcinoma, Genotype, medicine, Cancer research, Copy-number variation, Ovarian cancer, Carcinogenesis
Abstract: Ovarian cancer affects ∼ 204,000 women each year, and it is one of the leading causes of cancer-related death among women world-wide, as most patients present with advanced stage (III/IV) tumours, and only 40% survive 5 years after diagnosis. Improvement in the clinical management of ovarian patients is likely to derive from a better understanding of the molecular aberrations which initiate and maintain tumour growth as well as from the discovery of novel drug-able targets for the development of personalised targeted therapies. In this study, we comprehensively characterised the cancer genome of a patient diagnosed with grade III serous ovarian carcinoma, using a combination of massive-parallel sequencing technologies, including long distance DNA Paired-End-Tag (DNA-PET) sequencing, RNA-sequencing and exome-capture sequencing. This approach ensures deep coverage (from 50-180X) of critical mutational elements in a cancer genome. By comparing the genomic abnormalities identified in the tumour sample with those found in its normal counterpart (peripheral blood lymphocytes), we were able to compile a catalogue of all of the somatic events which occurred during oncogenesis and to define the overall complexity of this specific cancer genome. Interestingly, chromosomal arm loss appeared to be the predominant feature of this tumour, with more than 30% of the haploid genome being affected by a decrease in copy number. This associated with a prevalence of inter-chromosomal rearrangements, suggesting chromosomal translocations as a preferred consequence of genomic instability. Here we describe some examples of somatic translocation events causing the loss of tumour suppressor genes. Using this genotype as a possible model of ovarian carcinoma evolution, we aim to explain a subset of ovarian cancers displaying a similar chromosomal profile by applying an analysis of copy number variations, and to define common mechanisms of cancer gene loss. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5107. doi:1538-7445.AM2012-5107
Published: 2012

22. Whole-genome reconstruction and mutational signatures in gastric cancer

Author: Zhi Jiang Zang, Xiaoan Ruan, Brendan Pang, Axel M. Hillmer, Guillaume Bourque, Choon Kiat Ong, Denis Bertrand, Wing-Kin Sung, Chiea Chuen Khor, Audrey S.M. Teo, Ming Teh, Martin L. Hibberd, Patrick Tan, Pramila N. Ariyaratne, Kartiki V. Desai, Feng Zhu, Steven G. Rozen, Fei Yao, Pierre-Étienne Jacques, Niantao Deng, Jimmy Bok Yan So, Ioana Cutcutache, Jaideepraj Rao, Niranjan Nagarajan, Khay Guan Yeoh, Xing Yi Woo, Atif Shahab, Mengchu Wu, Lavanya Veeravali, Yijun Ruan, Zhenshui Zhang, Bin Tean Teh, Yee Yen Sia, Song Gao, Richie Soong, Wah Heng Lee, Sze Yung Chin, and Andrea Ho
Subjects: DNA Mutational Analysis, Computational biology, Adenocarcinoma, Biology, medicine.disease_cause, Stomach Neoplasms, Chromosomal Instability, Chromosome instability, medicine, Exome, Exome sequencing, Genetics, Research, High-Throughput Nucleotide Sequencing, Microsatellite instability, Cancer, Genomics, medicine.disease, digestive system diseases, Deamination, Mutation, Microsatellite Instability, KRAS, Reactive Oxygen Species, Carcinogenesis
Abstract: BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability. RESULTS: Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer--against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer. CONCLUSIONS: These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data.
Published: 2012

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22 results on '"Denis, Bertrand"'

1. P392: Rapid complement mediated TMA diagnosis and early intervention in a renal intensive care unit using Nanopore technology

2. Duration of Carbapenemase-Producing Enterobacteriaceae Carriage in Hospital Patients

3. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

4. Household transmission of carbapenemase-producing Enterobacteriaceae: a prospective cohort study

5. Genome Alert!: a standardized procedure for genomic variant reinterpretation and automated genotype-phenotype reassessment in clinical routine

6. ConsensusDriver Improves upon Individual Algorithms for Predicting Driver Alterations in Different Cancer Types and Individual Patients

7. Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time

8. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

9. Comprehensive Characterization of Cancer Driver Genes and Mutations

10. Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics

11. The pulmonary microbiome in non-cystic fibrosis bronchiectasis

12. Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

13. Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion

14. Cloning and variation of ground state intestinal stem cells

15. The Opisthorchis viverrini genome provides insights into life in the bile duct

16. Abstract 3414: Genomic signatures of melanoma maintenance

17. Abstract 3180: In vitro tool for discovering oncogenes and tumor suppressor genes in a system's manner

18. Abstract 2001: Genomic signatures of melanoma progression and maintenance

19. 585 Genomics of Metastatic Progression in Cutaneous Melanoma

20. 606 Defining the Molecular States of Cancer and Stem Cells Through Integrative Transcriptional and Genomic Analysis

21. Abstract 5107: Unravelling the complexity of individual cancer genomes

22. Whole-genome reconstruction and mutational signatures in gastric cancer

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22 results on '"Denis, Bertrand"'

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