The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element
Open accessAbstract
In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell’s transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB binds to this new site and recruits its H3K27 acetylase–binding partner CBP, as well as core components of a major leukemogenic transcriptional complex that contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super-enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a general role for MYB in super-enhancer initiation. Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells.
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“The ability of AlphaGenome to simultaneously score variant effects across all modalities accurately recapitulates the mechanisms of clinically relevant variants near the TAL1 oncogene6.”
From Advancing regulatory variant effect prediction with AlphaGenome (2026) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“Detailed ALT–REF predictions for an oncogenic insertion (chr. 1: 47239296: C>ACG) characterized in ref. 6. Shown are differences between AlphaGenome predictions between the ALT and REF sequences of the variant in CD34+ CMP tracks. The ALT sequence increases expression of the TAL1 gene 7.5 kb away.”
From Advancing regulatory variant effect prediction with AlphaGenome (2026) · cites this paper as [6]
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“We evaluated three groups of gain-of-function mutations affecting the TAL1 gene in T cell acute lymphoblastic leukaemia (T-ALL): a cluster of 5′ neo-enhancer mutations upstream of the TAL1 TSS6,33, an intronic single-nucleotide variant (SNV)34 and a 3′ neo-enhancer35.”
From Advancing regulatory variant effect prediction with AlphaGenome (2026) · cites this paper as [6]
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“By contrast, the alternative sequence introduced a MYB motif at the variant position predicted to increase TAL1 expression, chromatin accessibility and H3K27ac chromatin marks (Fig. 6e), as discovered previously6.”
From Advancing regulatory variant effect prediction with AlphaGenome (2026) · cites this paper as [6]
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Citations
Cites
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
DNA targeting specificity of RNA-guided Cas9 nucleases
Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., Li, Y., Fine, E. J., Wu, X., Shalem, O., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2647 · Cited by 4,741
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Self-citationSelective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143
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Items 801–805 of 805
A guide to transcriptional cyclin‐dependent kinases in cancer
Devlin, J. R., Kyheröinen, S., & Johnstone, R. W. (2026) · FEBS Journal · doi:10.1111/febs.70731
Single-allele nanoscale mapping of regulatory variants
Hamley, J. C., Zhang, W., Willmott, D., Chen, L., Sharlandjieva, V., Li, H., Dalgleish, J. L. T., Denny, N., Agarwal, G., Hentges, L. D., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02776-8
Untranslated region rewiring defines a novel class of oncogene fusions
Cerqua, M., Bigot, E., Chaveroux, C., Comoglio, P. M., & Altintas, D. M. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118145
Liang, Y., 徐小慧, Mao, Y., Zheng, Z., & Liu, N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.11.756618
de Barrios, O., Tejedor, J. R., & Parra, M. (2024) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.11550905
Metadata
- Authors
- Mansour, M. R., Abraham, B. J., Anders, L., Berezovskaya, A., Gutierrez, A., Durbin, A. D., Etchin, J., Lawton, L., Sallan, S. E., Silverman, L. B., Loh, M. L., Hunger, S. P., Sanda, T., Young, R. A., & Look, A. T.
- Affiliations
- Harvard University (US)
- Whitehead Institute for Biomedical Research (US)
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
- Boston Children's Hospital (US)
- University of California, San Francisco (US)
- Children's Hospital Colorado (US)
- National University of Singapore (SG)
- Corresponding author
- Abraham, Brian J.
- Anders, Lars
- Young, Richard A.
- Look, A. Thomas
- ORCID
- Venue
- Science
- Published
- 2014-12-12
- Volume
- 346
- Issue
- 6215
- Pages
- 1373-1377
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4720521
- OpenAlex
- W2082414039
- Cited by
- 801
- References
- 46
- Citations by year
- 2026: 32 · 2025: 49 · 2024: 61 · 2023: 77 · 2022: 84 · 2021: 85 · 2020: 80 · 2019: 62 · 2018: 65 · 2017: 77 · 2016: 76 · 2015: 49 · 2014: 4
- FWCI
- 28.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- UCL Discovery (University College London) (submittedVersion)
- PMC
- Funders
- National Human Genome Research Institute (R01HG002668)
- National Cancer Institute (R21CA167124, CA114766, CA30969, R01CA176746, CA‐98413, U10CA098413, U24CA114766, U10CA030969, P01CA068484, CA 29139, R01CA120215, 5P01CA68484, U10CA029139, U10CA098543, P01CA109901, CA167124, CA120215, CA-98543, P30CA014051)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
- Keywords
- super-enhancers, T-cell acute lymphoblastic leukemia, MYB transcription factors, somatic mutations, H3K27 acetylation, CBP, RUNX1, GATA3, transcriptional regulation, oncogene expression
- MeSH terms
- T-Cell Acute Lymphocytic Leukemia Protein 1, Acetylation, Base Sequence, Binding Sites, Enhancer Elements, Genetic, Histones, Humans, Molecular Sequence Data, Mutation, Oncogenes, Proto-Oncogene Proteins, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myb, DNA, Intergenic, Cell Line, Tumor, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, INDEL Mutation, Protein Interaction Domains and Motifs
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