The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma
Open accessAbstract
14-3-3 proteins are ubiquitously expressed regulators of various cellular functions, including proliferation, metabolism, and differentiation, and altered 14-3-3 expression is associated with development and progression of cancer. We report a transforming 14-3-3 oncoprotein, which we identified through conventional cytogenetics and whole-transcriptome sequencing analysis as a highly recurrent genetic mechanism in a clinically aggressive form of uterine sarcoma: high-grade endometrial stromal sarcoma (ESS). The 14-3-3 oncoprotein results from a t (10;17) genomic rearrangement, leading to fusion between 14-3-3ε (YWHAE) and either of two nearly identical FAM22 family members (FAM22A or FAM22B). Expression of YWHAE–FAM22 fusion oncoproteins was demonstrated by immunoblot in t (10;17)-bearing frozen tumor and cell line samples. YWHAE–FAM22 fusion gene knockdowns were performed with shRNAs and siRNAs targeting various FAM22A exons in an t (10;17)-bearing ESS cell line (ESS1): Fusion protein expression was inhibited, with corresponding reduction in cell growth and migration. YWHAE–FAM22 maintains a structurally and functionally intact 14-3-3ε (YWHAE) protein-binding domain, which is directed to the nucleus by a FAM22 nuclear localization sequence. In contrast to classic ESS, harboring JAZF1 genetic fusions, YWHAE–FAM22 ESS display high-grade histologic features, a distinct gene-expression profile, and a more aggressive clinical course. Fluorescence in situ hybridization analysis demonstrated absolute specificity of YWHAE–FAM22A/B genetic rearrangement for high-grade ESS, with no fusions detected in other uterine and nonuterine mesenchymal tumors (55 tumor types, n = 827). These discoveries reveal diagnostically and therapeutically relevant models for characterizing aberrant 14-3-3 oncogenic functions.
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Self-citationMutational evolution in a lobular breast tumour profiled at single nucleotide resolution
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Self-citationKIT activation is a ubiquitous feature of gastrointestinal stromal tumors.
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Self-citation14-3-3σ is required to prevent mitotic catastrophe after DNA damage
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Mutation of FOXL2 in Granulosa-Cell Tumors of the Ovary
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14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport
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Cited by
Casali, P. G., Abecassis, N., Bauer, S., Biagini, R., Bielack, S., Bonvalot, S., Boukovinas, I., Bovee, J. V. M. G., Brodowicz, T., Broto, J. M., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy096 · Cited by 1,614
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Astolfi, A., Fiore, M., Melchionda, F., Indio, V., Bertuccio, S. N., & Pession, A. (2019) · Epigenomics · doi:10.2217/epi-2018-0195 · Cited by 183
Metadata
- Authors
- Lee, C.-H., Ou, W.-B., Mariño-Enriquez, A., Zhu, M., Mayeda, M., Wang, Y., Guo, X., Brunner, A. L., Amant, F., French, C. A., West, R. B., McAlpine, J. N., Gilks, C. B., Yaffe, M. B., Prentice, L. M., McPherson, A., Jones, S. J. M., Marra, M. A., Shah, S. P., van de Rijn, M., Huntsman, D. G., Dal Cin, P., Debiec-Rychter, M., Nucci, M. R., & Fletcher, J. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2012-01-05
- Volume
- 109
- Issue
- 3
- Pages
- 929-934
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013189329
- Cited by
- 259
- References
- 28
- FWCI
- 22.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Lee, C.-H., Ou, W.-B., Mariño-Enriquez, A., Zhu, M., Mayeda, M., Wang, Y., Guo, X., Brunner, A. L., Amant, F., French, C. A., West, R. B., McAlpine, J. N., Gilks, C. B., Yaffe, M. B., Prentice, L. M., McPherson, A., Jones, S. J. M., Marra, M. A., Shah, S. P., . . . Fletcher, J. A. (2012). 14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1115528109
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