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Record W2126547130 · doi:10.1038/nature13480

Comprehensive molecular characterization of gastric adenocarcinoma

2014· article· en· W2126547130 on OpenAlexaff
Adam J. Bass, Natalie Tasman, Brady Bernard, Vésteinn Thórsson, Roger Kramer, Michael Miller, Ilya Shmulevich, Lisa Iype, Hector Rovira, Richard Kreisberg, Sheila M. Reynolds, Timothy J. Triche, Phillip H. Lai, Toshinori Hinoue, Hui Shen, Daniel J. Weisenberger, David Van Den Berg, Peter W. Laird, Christina Curtis, Nikolaus Schultz, Jianjiong Gao, Nils Weinhold, Yasin Şenbabaoğlu, Rileen Sinha, Benjamin Groß, Gideon Dresdner, Ricardo Ramírez, Chris Sander, S. Onur Sumer, William Lee, Giovanni Ciriello, Yichao Sun, Ronglai Shen, Yelena Y. Janjigian, David P. Kelsen, Haiyan A. Li, Amanda Clarke, Noreen Dhalla, Andy Chu, Andrew J. Mungall, Justin Chu, Nina Thiessen, Karen Mungall, Emilia L. Lim, Denise Brooks, Reanne Bowlby, Miruna Balasundaram, Darlene Lee, Angela Tam, Richard A. Moore, Hye-Jung E. Chun, Michael Mayo, A. Gordon Robertson, Eric Chuah, Steven J.M. Jones, Rebecca Carlsen, Marco A. Marra, Payal Sipahimalani, Yussanne Ma, Ranabir Guin, Robert A. Holt, Yaron S.N. Butterfield, Ka Ming Nip, Adrian Ally, Jacqueline E. Schein, İnanç Birol, Lihua Zou, Nils Gehlenborg, Yingchun Liu, Travis Zack, Scott L. Carter, Jaegil Kim, Eric S. Lander, Petar Stojanov, Barbara Tabak, Andrew D. Cherniack, Gordon Saksena, Bradley A. Murray, Rameen Beroukhim, Lee Lichtenstein, Carrie Sougnez, Gad Getz, Chandra Sekhar Pedamallu, Juok Cho, Kristian Cibulskis, David I. Heiman, Doug Voet, Joonil Jung, Sheila Fisher, Hailei Zhang, Scott Frazer, Michael S. Lawrence, Pei Lin, Daniel DiCara, Matthew Meyerson, Stacey Gabriel, Amaro Taylor‐Weiner, Michael S. Noble, Steven E. Schumacher, Mara Rosenberg, Akinyemi I. Ojesina, Ju‐Seog Lee, Arvind Rao, John N. Weinstein, Rehan Akbani, Shiyun Ling, Wenbin Liu, Sangbae Kim, Gordon B. Mills, Yiling Lu, Wei Zhang, Da Yang, Jonathan G. Seidman, Netty Santoso, Raju Kucherlapati, Angeliki Pantazi, Xiaojia Ren, Angela Hadjipanayis, Michael Parfenov, Margaret L. Gulley, Barbara Schneider, M. Blanca Piazuelo, Young S. Park, Jihun Kim, Alex Boussioutas, Roy Tarnuzzer, Margi Sheth, Greg Eley, Zhining Wang, John A. Demchok, Jean C. Zenklusen, Liming Yang, Kenna Shaw, Charles S. Rabkin, M. Constanza Camargo, Joseph Willis, David Haussler, Sam Ng, Joshua M. Stuart, Katherine S. Garman, David G. Beer, Rodney J. Landreneau, Rajiv Dhir, Arjun Pennathur, James D. Luketich, Benjamin J. Raphael, Hsin-Ta Wu, Mark D.M. Leiserson, Robert D. Odze, Hark K. Kim, Teresa R. Tabler, Kristen Leraas, Tara M. Lichtenberg, Erik Zmuda, Aaron D. Black, Cynthia McAllister, Jay Bowen, Carmen Helsel, Julie M. Gastier-Foster, J A Carney, Stephanie Weaver, Nilsa C. Ramirez, Lisa Wise, Beifang Niu, Li Ding, Michael D. McLellan, Matthew Ibbs, Ewa Leporowska, Wiktoria Maria Suchorska, Witold Kycler, Maciej Wiznerowicz, Honorata Tatka, Konstanty Korski, Andrzej Maćkiewicz, Arkadiusz Spychała, Jakub Brzezinski, M. Teresiak, Dawid Murawa, P. Murawa, Ryo Sakai, Roeland Verhaak, Sahil Seth, Christopher A. Bristow, Lynda Chin, Harshad S. Mahadeshwar, Xingzhi Song, Jiabin Tang, Alexei Protopopov, Jianhua Zhang, Semin Lee, Lixing Yang, Ruibin Xi, Peter J. Park, Andrew Wei Xu, Stephen B. Baylin, James G. Herman, Barry S. Taylor, Scott Morris, Ariane Kemkes, Kevin Lau, Troy Shelton, Joseph Paulauskis, Erin Curely, Johanna Gardner, Daniel Crain, Erin Curley, Mark E. Sherman, David Mallery, Robert Penny, Christopher C. Benz, Jae-Hyuk Lee, Konstantin Fedosenko, Georgy M. Manikhas, Olga Potapova, O V Dolzhansky, Olga Voronina, W. Kimryn Rathmell, Jennifer R. Brown, Raafat Abdel‐Misih, Brenda Rabeno, Joseph Bennett, Mary Iacocca, Sun Young Kwon, Iakovina Alexopoulou, Jay Engel, John M.S. Bartlett, Monique Albert, Do-Youn Park, Laura H. Tang, Marc Ladanyi

Bibliographic record

VenueNature · 2014
Typearticle
Languageen
FieldMedicine
TopicCholangiocarcinoma and Gallbladder Cancer Studies
Canadian institutionsKingston General HospitalOntario Institute for Cancer ResearchUniversity of British ColumbiaSt. Joseph’s Healthcare HamiltonCanada's Michael Smith Genome Sciences CentreQueen's University
FundersNational Cancer InstituteNational Human Genome Research InstituteNational Institutes of Health
KeywordsMicrosatellite instabilityCancer researchChromosome instabilityBiologyCancerTargeted therapyAdenocarcinomaRHOAGeneMutationGeneticsChromosomeSignal transductionMicrosatellite

Abstract

fetched live from OpenAlex

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies. This contribution from The Cancer Genome Atlas (TCGA) project describes the molecular evaluation of 295 primary gastric adenocarcinomas. Based on the results, the authors propose a novel classification separating gastric cancers into four subtypes according to: Epstein–Barr virus positive status, microsatellite instability, chromosomal instability or genomic stability. Given the histologic and etiologic heterogeneity of gastric cancer identification of these subtypes, using a schema that can readily be applied to patient samples should help with patient stratification and trials of targeted therapies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0030.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.249
Teacher spread0.241 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations6,505
Published2014
Admission routes1
Has abstractyes

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