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Record W3049139822 · doi:10.1038/s41467-020-17917-8

Genomic characterization of malignant progression in neoplastic pancreatic cysts

2020· article· en· W3049139822 on OpenAlexaff
Michaël Noë, Noushin Niknafs, Catherine G. Fischer, Wenzel M. Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R. White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, M. Paola Castelli, Seung‐Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J. Gill, Jaswinder S. Samra, G. Johan A. Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, Volkan Adsay, Wei Jiang, Jordan M. Winter, Jorge Albores‐Saavedra, Benoît Terris, Elizabeth D. Thompson, Nicholas J. Roberts, Ralph H. Hruban, Rachel Karchin, Robert B. Scharpf, Lodewijk A.A. Brosens, Victor E. Velculescu, Laura D. Wood

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicPancreatic and Hepatic Oncology Research
Canadian institutionsPancreas Centre (Canada)
FundersPanKind, The Australian Pancreatic Cancer FoundationLisa Waller Hayes FoundationEmerson CollectiveNational Cancer InstituteNational Institutes of HealthIncyteRolfe Pancreatic Cancer FoundationGerald O. Mann Charitable FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesSidney Kimmel Foundation for Cancer ResearchDr. Miriam and Sheldon G. Adelson Medical Research Foundation
KeywordsDysplasiaPancreatic cancerIntraductal papillary mucinous neoplasmBiologyExome sequencingMalignant transformationPathologyAdenocarcinomaCancerCancer researchPancreasMedicineMutationGeneGeneticsEndocrinology

Abstract

fetched live from OpenAlex

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three years between the development of high-grade dysplasia and pancreatic cancer. Taken together, these data establish non-invasive IPMNs and MCNs as origins of invasive pancreatic cancer, identifying potential drivers of invasion, highlighting the complex clonal dynamics prior to malignant transformation, and providing opportunities for early detection and intervention.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
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 head0.038
GPT teacher head0.364
Teacher spread0.325 · 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 designBench or experimental
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

Citations137
Published2020
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicPancreatic and Hepatic Oncology ResearchFrench-language works237,207