The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development
Open accessAbstract
The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell–activating pathways.
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Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
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Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma
Morin, R. D., Mendez-Lago, M., Mungall, A. J., Goya, R., Mungall, K. L., Corbett, R. D., Johnson, N. A., Severson, T. M., Chiu, R., Field, M., et al. (2011) · Nature · doi:10.1038/nature10351 · Cited by 1,614
Self-citationLee, J.-E., Wang, C., Xu, S., Cho, Y.-W., Wang, L., Feng, X., Baldridge, A., Sartorelli, V., Zhuang, L., Peng, W., et al. (2013) · eLife · doi:10.7554/elife.01503 · Cited by 522
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Cited by
Chapuy, B., Stewart, C., Dunford, A. J., Kim, J., Kamburov, A., Redd, R. A., Lawrence, M. S., Roemer, M. G. M., Li, A. J., Ziepert, M., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0016-8 · Cited by 1,941
Epigenetic balance of gene expression by Polycomb and COMPASS families
Piunti, A., & Shilatifard, A. (2016) · Science · doi:10.1126/science.aad9780 · Cited by 524
Self-citationEnnishi, D., Takata, K., Béguelin, W., Duns, G., Mottok, A., Farinha, P., Bashashati, A., Saberi, S., Boyle, M., Meissner, B., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1090 · Cited by 318
“Detailed data analysis was previously described (47).”
MethodHistone H3 lysine 4 methyltransferase KMT2D
Froimchuk, E., Jang, Y., & Ge, K. (2017) · Gene · doi:10.1016/j.gene.2017.06.056 · Cited by 299
Self-citationGenetics of diffuse large B-cell lymphoma
Pasqualucci, L., & Dalla-Favera, R. (2018) · Blood · doi:10.1182/blood-2017-11-764332 · Cited by 282
Metadata
- Authors
- Ortega-Molina, A., Boss, I. W., Canela, A., Pan, H., Jiang, Y., Zhao, C., Jiang, M., Hu, D., Agirre, X., Niesvizky, I., Lee, J.-E., Chen, H.-T., Ennishi, D., Scott, D. W., Mottok, A., Hother, C., Liu, S., Cao, X.-J., Tam, W., Shaknovich, R., Garcia, B. A., Gascoyne, R. D., Ge, K., Shilatifard, A., Elemento, O., Nussenzweig, A., Melnick, A. M., & Wendel, H.-G.
- Venue
- Nature Medicine
- Published
- 2015-09-14
- Volume
- 21
- Issue
- 10
- Pages
- 1199-1208
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2214176334
- Cited by
- 436
- References
- 5
- FWCI
- 23.40
- Type
- journal article
- Language
- en
- Open access
- green
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- Ortega-Molina, A., Boss, I. W., Canela, A., Pan, H., Jiang, Y., Zhao, C., Jiang, M., Hu, D., Agirre, X., Niesvizky, I., Lee, J.-E., Chen, H.-T., Ennishi, D., Scott, D. W., Mottok, A., Hother, C., Liu, S., Cao, X.-J., Tam, W., . . . Wendel, H.-G. (2015). The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nature Medicine. https://doi.org/10.1038/nm.3943
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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