The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development
Open accessAbstract
Splenic marginal zone lymphoma (SMZL) is a B cell malignancy of unknown pathogenesis, and thus an orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis, we show that the SMZL exome carries at least 30 nonsilent gene alterations. Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting for ∼20% of cases. All NOTCH2 mutations are predicted to cause impaired degradation of the NOTCH2 protein by eliminating the C-terminal PEST domain, which is required for proteasomal recruitment. Among indolent B cell lymphoproliferative disorders, NOTCH2 mutations are restricted to SMZL, thus representing a potential diagnostic marker for this lymphoma type. In addition to NOTCH2, other modulators or members of the NOTCH pathway are recurrently targeted by genetic lesions in SMZL; these include NOTCH1, SPEN, and DTX1. We also noted mutations in other signaling pathways normally involved in MZ B cell development, suggesting that deregulation of MZ B cell development pathways plays a role in the pathogenesis of ∼60% SMZL. These findings have direct implications for the treatment of SMZL patients, given the availability of drugs that can target NOTCH, NF-κB, and other pathways deregulated in this disease.
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Cites
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Metadata
- Authors
- Rossi, D., Trifonov, V., Fangazio, M., Bruscaggin, A., Rasi, S., Spina, V., Monti, S., Vaisitti, T., Arruga, F., Famà, R., Ciardullo, C., Greco, M., Cresta, S., Piranda, D., Holmes, A., Fabbri, G., Messina, M., Rinaldi, A., Wang, J., Agostinelli, C., Piccaluga, P. P., Lucioni, M., Tabbò, F., Serra, R., Franceschetti, S., Deambrogi, C., Daniele, G., Gattei, V., Marasca, R., Facchetti, F., Arcaini, L., Inghirami, G., Bertoni, F., Pileri, S. A., Deaglio, S., Foà, R., Dalla-Favera, R., Pasqualucci, L., Rabadan, R., & Gaidano, G.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2012-08-13
- Volume
- 209
- Issue
- 9
- Pages
- 1537-1551
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2147253462
- Cited by
- 379
- References
- 55
- FWCI
- 22.24
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rossi, D., Trifonov, V., Fangazio, M., Bruscaggin, A., Rasi, S., Spina, V., Monti, S., Vaisitti, T., Arruga, F., Famà, R., Ciardullo, C., Greco, M., Cresta, S., Piranda, D., Holmes, A., Fabbri, G., Messina, M., Rinaldi, A., Wang, J., . . . Gaidano, G. (2012). The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20120904
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