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Record W4382062614 · doi:10.3390/cancers15133313

Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases

2023· article· en· W4382062614 on OpenAlexafffund
Gisella Figlioli, Amandine Billaud, Qin Wang, Manjeet K. Bolla, Joe Dennis, Michael Lush, Anders Kvist, Muriel A. Adank, Thomas U. Ahearn, Natalia Antonenkova, Päivi Auvinen, Sabine Behrens, Marina Bermisheva, Natalia Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Thomas Brüning, Nicola J. Camp, Archie Campbell, Jose E. Castelao, Melissa H. Cessna, Kamila Czene, Peter Devilee, Thilo Dörk, Mikael Eriksson, Peter A. Fasching, Henrik Flyger, Marike Gabrielson, Manuela Gago-Domínguez, Montserrat García‐Closas, Gord Glendon, E. Gómez, Anna González‐Neira, Felix Graßmann, Pascal Guénel, Eric Hahnen, Ute Hamann, Peter Hillemanns, Maartje J. Hooning, Reiner Hoppe, Anthony Howell, Keith Humphreys, Anna Jakubowska, Э. К. Хуснутдинова, Vessela N. Kristensen, Annika Lindblom, Maria A. Loizidou, Jan Lubiński, Tabea Maurer, Dimitrios Mavroudis, William G. Newman, Nadia Obi, Mihalis I. Panayiotidis, Paolo Radice, Muhammad Usman Rashid, Valerie Rhenius, Matthias Ruebner, Emmanouil Saloustros, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Mitul Shah, Melissa C. Southey, Ian Tomlinson, Thérèse Truong, Elke M. van Veen, Camilla Wendt, Xiaohong R. Yang, Kyriaki Michailidou, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Irene L. Andrulis, D. Gareth Evans, Antoinette Hollestelle, Jenny Chang‐Claude, Roger L. Milne, Paolo Peterlongo

Bibliographic record

VenueCancers · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsUniversity of TorontoLunenfeld-Tanenbaum Research InstituteUniversity Health NetworkMount Sinai Hospital
FundersMedical Research and Materiel CommandServicio Gallego de SaludInstituto de Salud Carlos IIICancer Council TasmaniaCancer Council South AustraliaNational Health and Medical Research CouncilMedical Research CouncilCanadian Institutes of Health ResearchProgramme Grants for Applied ResearchManchester Biomedical Research CentreU.S. ArmyNational Institutes of HealthCancer Council VictoriaMinistry of Science and Higher Education of the Russian FederationSyöpäsäätiöAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailXunta de GaliciaFondazione Italiana per la Ricerca sul CancroDeutsche KrebshilfeMedizinischen Hochschule HannoverCenters for Disease Control and PreventionInstitut National Du CancerLeids Universitair Medisch CentrumAssociazione Italiana per la Ricerca sul CancroFondazione Umberto VeronesiKWF KankerbestrijdingUniversity of CreteStockholms Läns LandstingLigue Contre le CancerKuopion Yliopistollinen SairaalaKarolinska InstitutetGentofte HospitalDeutsche Gesetzliche UnfallversicherungDeutsche ForschungsgemeinschaftNederlandse Organisatie voor Wetenschappelijk OnderzoekRussian Foundation for Basic ResearchUniversiteit LeidenCancer AustraliaAgence Nationale de la RechercheHuntsman Cancer FoundationRobert Bosch StiftungAgency for Science, Technology and ResearchCancerfondenNational Cancer InstituteCancer Institute NSWCancer Council Western AustraliaEuropean CommissionMinisterio de Sanidad, Servicios Sociales e IgualdadGovernment of CanadaUniversity of CambridgeFondation de FranceUniversity of UtahNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchWellcome TrustFondation du cancer du sein du QuébecFreistaat SachsenHuntsman Cancer InstituteHamburger KrebsgesellschaftCancer Research UKKing’s College LondonScottish Funding CouncilSusan G. KomenChief Scientist Office, Scottish Government Health and Social Care DirectorateBundesministerium für Bildung und ForschungNational Breast Cancer FoundationTranscanDeutsches KrebsforschungszentrumSundhed og Sygdom, Det Frie ForskningsrådConsejo Nacional de Ciencia y TecnologíaNorges ForskningsrådDivision of Cancer Prevention, National Cancer InstituteScottish GovernmentIntermountain HealthcareGenome CanadaItä-Suomen YliopistoKreftforeningenUddannelses- og ForskningsministerietGesellschaft der Freunde der Medizinischen Hochschule HannoverResearch Promotion FoundationEuropean Regional Development FundKing's College LondonCancer Council NSWSusan G. Komen for the CureNational Institute for Health and Care ResearchMinisterie van Volksgezondheid, Welzijn en SportU.S. Department of Health and Human Services
KeywordsGermlineBreast cancerCancerCohortMedicineFounder effectOncologyBiologyInternal medicineGeneticsGeneGenotype

Abstract

fetched live from OpenAlex

FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.017
GPT teacher head0.281
Teacher spread0.264 · 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

Citations1
Published2023
Admission routes2
Has abstractyes

Explore more

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