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Record W4403378905 · doi:10.1038/s41375-024-02363-y

Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14)

2024· article· en· W4403378905 on OpenAlexaff
Hongwei Tang, Huihuang Yan, Suganti Shivaram, Stacey L. Lehman, Neeraj Sharma, James B. Smadbeck, Cinthya Zepeda‐Mendoza, Shulan Tian, Yan W. Asmann, Celine M. Vachon, Alexandre Gaspar‐Maia, Jonathan J. Keats, P. Leif Bergsagel, Rafaël Fonseca, A. Keith Stewart, Joel-Sean Hsu, Richard K. Kandasamy, Akhilesh Pandey, Marcella Kaddoura, Francesco Maura, Amit Mitra, S. Vincent Rajkumar, Shaji Kumar, Eran Elhaik, Esteban Braggio, Linda B. Baughn

Bibliographic record

VenueLeukemia · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsPrincess Margaret Cancer Centre
FundersNational Cancer InstituteNational Institutes of HealthDivision of Cancer Epidemiology and Genetics, National Cancer InstituteMayo ClinicU.S. Department of Health and Human Services
KeywordsMultiple myelomaCancer researchHematologyBiologyInternal medicineImmunologyPathologyMedicineComputational biology

Abstract

fetched live from OpenAlex

Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). Sequencing data from 2 independent cohorts, CoMMpass (n = 698) and Mayo Clinic (n = 661), confirm the positive association between the G allele and t(11;14). Among 80% of individuals heterozygous for rs9344 with t(11;14), the t(11;14) event occurs on the G allele, demonstrating a biological preference for the G allele in t(11;14). Within t(11;14), the G allele is associated with higher CCND1 expression and elevated H3K27ac and H3K4me3. CRISPR/Cas9 mediated A to G conversion resulted in increased H3K27ac over CCND1 and elevated CCND1 expression. ENCODE ChIP-seq data supported a PAX5 binding site within the enhancer region covering rs9344, showing preferential binding to the G allele. Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.153
Threshold uncertainty score0.461

Codex and Gemma teacher scores by category

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

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 head0.209
Teacher spread0.200 · 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 teacher head, 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

Citations1
Published2024
Admission routes1
Has abstractyes

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